# US 2021/0277119 A1 · Anti-tcr antibody molecules and uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2021/0277119 A1
- Document ID: US20210277119A1
- Status: Published application
- Kind: A1
- Application number: 17/256,917
- Filed: 2019-07-03
- Published: 2021-09-09
- Earliest claimed: 2018-07-03
- Assignees: Elstar Therapeutics, Inc.
- Applicants: Elstar Therapeutics, Inc.
- Inventors: Seng-Lai TAN; Brian Edward VASH; Jonathan HSU; Dilini Charmain GUNASEKERA; Sangeetha Sagar PALAKURTHI; Andreas LOEW
- Web page: https://patentgrep.com/patent/US20210277119A1

## CPC

- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 40/10: characterised by the cell type used
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/4211: {CD19 or B4}
- A61K 40/4215: {Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30}
- A61P 35/00: Antineoplastic agents
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/283: {against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851)}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C12N 5/0634: {Cells from the blood or the immune system}
- A61K 2039/505: {comprising antibodies}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/55: Fab or Fab'
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The disclosure provides antibody molecules that bind to TCR Vβ regions and multispecific molecules comprising said antibody molecules. Additionally, disclosed are nucleic acids encoding the same, methods of producing the aforesaid molecules, pharmaceutical compositions comprising aforesaid molecules, and methods of treating a cancer using the aforesaid molecules.

## Claims

### Claim 1

A multispecific molecule (e.g., a bispecific molecule), comprising a first moiety (e.g., a first immune cell engager) comprising an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”).

### Claim 2 (depends on 1)

The multispecific molecule of claim 1, comprising a second moiety which comprises one or more of: a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an anti-TCRβV antibody molecule other than the first moiety.

### Claim 3 (depends on 1, 2)

The multispecific molecule of claim 1 or 2, wherein binding of the first moiety to the TCRβV region results in a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCRβV region (“a non-TCRβV-binding T cell engager”).

### Claim 4 (depends on 3)

The multispecific molecule of claim 3, wherein the non-TCRβV-binding T cell engager comprises an antibody that binds to a CD3 molecule (e.g., CD3 epsilon (CD3e) molecule); or a TCR alpha (TCRα) molecule.

### Claim 5 (depends on 3, 4)

The multispecific molecule of claim 3 or 4, wherein the cytokine profile of the first moiety comprises, one, two, three, four, five, six, seven, or all of the following:
(i) increased level, e.g., expression level, and/or activity of IL-2;
(ii) reduced level, e.g., expression level, and/or activity of IL-1β;
(iii) reduced level, e.g., expression level, and/or activity of IL-6;
(iv) reduced level, e.g., expression level, and/or activity of TNFα;
(v) reduced level, e.g., expression level, and/or activity of IL-10;
(vi) a delay, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more hours delay, in increased level, e.g., expression level, and/or activity of IL-2;
(vii) a delay, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 hours delay, in increased level, e.g., expression level, and/or activity of IFNg; or
(viii) increased level, e.g., expression level, and/or activity of IL-15,
e.g., wherein (i)-(viii) are relative to the cytokine profile of the non-TCRβV-binding T cell engager.

### Claim 6

The multispecific molecule of any of the preceding claims, wherein binding of the first moiety to the TCRβV region results in reduced cytokine storm, e.g., reduced cytokine release syndrome (CRS), as measured by an assay of Example 3, e.g., relative to the cytokine storm induced by the non-TCRβV-binding T cell engager.

### Claim 7

The multispecific molecule of any of the preceding claims, wherein binding of the first moiety to the TCRβV region results in one, two, three or all of:
(ix) reduced T cell proliferation kinetics;
(x) cell killing, e.g., target cell killing, e.g. cancer cell killing, e.g., as measured by an assay of Example 4;
(xi) increased Natural Killer (NK) cell proliferation, e.g., expansion; or
(xii) expansion, e.g., at least about 1.1-10 fold expansion (e.g., at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion), of a population of memory T cells,
e.g., wherein (ix)-(xii) are relative to the non-TCRβV-binding T cell engager.

### Claim 8 (depends on 7)

The multispecific molecule of claim 7, wherein the population of memory T cells comprises T effector memory (TEM) cells, e.g., TEM cells expressing CD45RA (TEMRA) cells.

### Claim 9

The multispecific molecule of any of the preceding claims, wherein the first moiety binds to one or more of a TCRβV subfamily chosen from:
(i) TCRβV6 subfamily comprising, e.g., one or more of TCRβV6-4*01, TCRβV6-4*02, TCRβV6-9*01, TCRβV6-8*01, TCRβV6-5*01, TCRβV6-6*02, TCRβV6-6*01, TCRβV6-2*01, TCRβV6-3*01 or TCRβV6-1*01;
(ii) TCRβV10 subfamily comprising, e.g., one or more of TCRβV10-1*01, TCRβV10-1*02, TCRβV10-3*01 or TCRβV10-2*01;
(iii) TCRβV5 subfamily comprising, e.g., one or more of TCRβV5-6*01, TCRβV5-4*01, or TCRβV5-8*01; or
(iv) TCRβV12 subfamily comprising, e.g., one or more of TCRβV12-4*01, TCRβV12-3*01, or TCRβV12-5*01.

### Claim 10

The multispecific molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule:
(i) binds specifically to an epitope on TCRβV, e.g., the same or similar epitope as the epitope recognized by an anti-TCRβV antibody molecule as described herein, e.g., a second anti-TCRβV antibody molecule;
(ii) shows the same or similar binding affinity or specificity, or both, as an anti-TCRβV antibody molecule as described herein, e.g., a second anti-TCRβV antibody molecule;
(iii) inhibits, e.g., competitively inhibits, the binding of an anti-TCRβV antibody molecule as described herein, e.g., a second anti-TCRβV antibody molecule;
(iv) binds the same or an overlapping epitope with an anti-TCRβV antibody molecule as described herein, e.g., a second anti-TCRβV antibody molecule; or
(v) competes for binding, and/or binds the same epitope, with an anti-TCRβV antibody molecule as described herein, e.g., a second anti-TCRβV antibody molecule,
wherein the second anti-TCRβV antibody molecule comprises an antigen binding domain comprising a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2) and/or a heavy chain complementarity determining region 3 (HC CDR3) of SEQ ID NO: 1 or SEQ ID NO: 9; and/or a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and/or a light chain complementarity determining region 3 (LC CDR3) of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11.

### Claim 11

The multispecific molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(i) (a) a HC CDR1, a HC CDR2 and/or a HC CDR3 of SEQ ID NO: 15, SEQ ID NO: 23, SEQ ID NO: 24 or SEQ IC NO: 25; and/or (b) a LC CDR1, a LC CDR2, and/or a LC CDR3 of SEQ ID NO: 16, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO:30; or
(ii) (a) a LC CDR1, a LC CDR2 and/or a LC CDR3 of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11; and/or (b) a HC CDR1, a HC CDR2 and/or a HC CDR2 of SEQ ID NO: 1 or SEQ ID NO: 9.

### Claim 12

The multispecific molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule binds the same or different TCRβV subfamily members.

### Claim 13

The multispecific molecule of any of the preceding claims, which comprises an antibody molecule chosen from a bispecific antibody molecule, a bivalent antibody molecule, or a biparatopic antibody molecule.

### Claim 14

The multispecific molecule of any of the preceding claims, which comprises a bispecific antibody molecule that binds to two different TCRβV subfamily members.

### Claim 15

The multispecific molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule binds:
(i) one or more of a TCRβV6 subfamily member and one or more of a TCRβV10 subfamily member;
(ii) one or more of a TCRβV6 subfamily member and one or more of a TCRβV5 subfamily member;
(iii) one or more of a TCRβV6 subfamily member and one or more of a TCRβV12 subfamily member;
(iv) one or more of a TCRβV10 subfamily member and one or more of a TCRβV5 subfamily member;
(v) one or more of a TCRβV10 subfamily member and one or more of a TCRβV12 subfamily member; or
(vi) one or more of a TCRβV5 subfamily member and one or more of a TCRβV12 subfamily member.

### Claim 16 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52)

A multispecific molecule, e.g., a bispecific molecule, comprising the anti-TCRβV antibody molecule of any of claims 17-52.

### Claim 17

An antibody molecule which binds, e.g., specifically binds, to a T cell receptor beta variable chain (TCRβV) region, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(a) a light chain variable region (VL) comprising:
(i) one, two or all of (e.g., three) a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and a light chain complementarity determining region 3 (LC CDR3) of SEQ ID NO: 10 or SEQ ID NO: 11; and
(ii) a framework region (FR) having at least 95% identity with one, two, three, or all of (e.g., four) a non-murine germline framework 1 (FR1), a non-murine germline framework region 2 (FR2), a non-murine germline framework region 3 (FR3), and a non-murine germline framework region 4 (FR4); and/or
(b) a heavy chain variable region (VH) comprising:
(i) one, two or all of (e.g., three) a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2) and a heavy chain complementarity determining region 3 (HC CDR3) of SEQ ID NO: 9; and
(ii) a framework region (FR) having at least 95% identity with one, two, three, or all of (e.g., four) a non-murine germline framework 1 (FR1), a non-murine germline framework region 2 (FR2), a non-murine germline framework region 3 (FR3), and a non-murine germline framework region 4 (FR4).

### Claim 18 (depends on 17)

The anti-TCRβV antibody molecule of claim 17, wherein the VL comprises an amino acid sequence having a consensus sequence of SEQ ID NO: 230.

### Claim 19 (depends on 17, 18)

The anti-TCRβV antibody molecule of claim 17 or 18, wherein the VH comprises an amino acid sequence having a consensus sequence of SEQ ID NO: 231.

### Claim 20 (depends on 17, 18, 19)

The anti-TCRβV antibody molecule of any of claims 17-19, which binds to TCRβV6, e.g., one or more of TCRβV6-4*01, TCRβV6-4*02, TCRβV6-9*01, TCRβV6-8*01, TCRβV6-5*01, TCRβV6-6*02, TCRβV6-6*01, TCRβV6-2*01, TCRβV6-3*01 or TCRβV6-1*01, or a variant thereof.

### Claim 21 (depends on 17, 18, 19, 20)

The anti-TCRβV antibody molecule of any of claims 17-20, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(i) a HC CDR1, a HC CDR2 and a HC CDR3 of SEQ ID NO: 1 or SEQ ID NO: 9, or an amino acid sequence listed in Table 1; or
(ii) a LC CDR1, a LC CDR2, and a LC CDR3 of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11, or an amino acid sequence listed in Table 1.

### Claim 22 (depends on 17, 18, 19, 20, 21)

The anti-TCRβV antibody molecule of any of claims 17-21, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all (e.g., three) of a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11, or an amino acid sequence listed in Table 1.

### Claim 23 (depends on 17, 18, 19, 20, 21, 22)

The anti-TCRβV antibody molecule of any of claims 17-22, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising a heavy chain variable region (VH) comprising one, two or all (e.g., three) of a HC CDR1, a HC CDR2 and a HC CDR3 of SEQ ID NO:1 or SEQ ID NO: 9, or an amino acid sequence listed in Table 1.

### Claim 24 (depends on 17, 18, 19, 20, 21, 22, 23)

The anti-TCRβV antibody molecule of any of claims 17-23, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(i) a VL comprising: a LC CDR1 amino acid sequence of SEQ ID NO: 6 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), a LC CDR2 amino acid sequence of SEQ ID NO:7 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), and/or a LC CDR3 amino acid sequence of SEQ ID NO:8 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof); and/or
(ii) a VH comprising: a HC CDR1 amino acid sequence of SEQ ID NO: 3 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), a HC CDR2 amino acid sequence of SEQ ID NO:4 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), and/or a HC CDR3 amino acid sequence of SEQ ID NO:5 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof).

### Claim 25 (depends on 17, 18, 19, 20, 21, 22, 23, 24)

The anti-TCRβV antibody molecule of any of claims 17-24, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
a variable heavy chain (VH) of an amino acid sequence listed in Table 1, e.g., SEQ ID NO: 9, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity to an amino acid sequence listed in Table 1, e.g., SEQ ID NO: 9; and/or
a variable light chain (VL) of an amino acid sequence listed in Table 1, e.g., SEQ ID NO: 10 or SEQ ID NO: 11, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity to an amino acid sequence listed in Table 1, e.g., SEQ ID NO: 10 or SEQ ID NO: 11.

### Claim 26 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25)

The anti-TCRβV antibody molecule of any of claims 17-25, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(i) the VH amino acid sequence of SEQ ID NO: 9;
(ii) an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 9;
(iii) the VL amino acid sequence of SEQ ID NO: 10; and/or
(iv) an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 10.

### Claim 27 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26)

The anti-TCRβV antibody molecule of any of claims 17-26, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(i) the VH amino acid sequence of SEQ ID NO: 9;
(ii) an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 9;
(iii) the VL amino acid sequence of SEQ ID NO: 11; and/or
(iv) an amino acid sequence having at least about 85%, 90%, 95%, or 99% sequence identity to the amino acid sequence of SEQ ID NO: 11.

### Claim 28 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)

The anti-TCRβV antibody molecule of any of claims 17-27, wherein the anti-TCRβV antibody molecule comprises a heavy chain comprising a framework region, e.g., framework region 3 (FR3), comprising one or both of:
(i) a Threonine at position 73, e.g., a substitution at position 73 according to Kabat numbering, e.g., a Glutamic Acid to Threonine substitution; or
(ii) a Glycine a position 94, e.g., a substitution at position 94 according to Kabat numbering, e.g., a Arginine to Glycine substitution;
wherein the substitution is relative to a human germline heavy chain framework region sequence.

### Claim 29 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28)

The anti-TCRβV antibody molecule of any of claims 17-28, wherein the anti-TCRβV antibody molecule comprises a light chain comprising a framework region, e.g., framework region 1 (FR1), comprising a Phenyalanine at position 10, e.g., a substitution at position 10 according to Kabat numbering, e.g., a Serine to Phenyalanine substitution, wherein the substitution is relative to a human germline light chain framework region sequence.

### Claim 30 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)

The anti-TCRβV antibody molecule of any of claims 17-29, wherein the anti-TCRβV antibody molecule comprises a light chain comprising a framework region, e.g., framework region 2 (FR2), comprising one or both of:
(i) a Histidine at position 36, e.g., a substitution at position 36 according to Kabat numbering, e.g., a Tyrosine to Histidine substitution; or
(ii) an Alanine at position 46, e.g., a substitution at position 46 according to Kabat numbering, e.g., a Arginine to Alanine substitution;
wherein the substitution is relative to a human germline light chain framework region sequence.

### Claim 31 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)

The anti-TCRβV antibody molecule of any of claims 17-30, wherein the anti-TCRβV antibody molecule comprises a light chain comprising a framework region, e.g., framework region 3 (FR3), comprising a Phenyalanine at position 87, e.g., a substitution at position 87 according to Kabat numbering, e.g., a Tyrosine to Phenyalanine substitution, wherein the substitution is relative to a human germline light chain framework region sequence.

### Claim 32

An antibody molecule which binds, e.g., specifically binds, to a T cell receptor beta variable chain (TCRβV) region, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(a) a light chain variable region (VL) comprising:
(i) one, two or all of (e.g., three) a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and a light chain complementarity determining region 3 (LC CDR3) of a humanized B-H light chain (LC) of Table 2; and
(ii) a framework region (FR) having at least 95% identity with one, two, three or all (e.g., four) of a framework region 1 (FR1), a framework region 2 (FR2), a framework region 3 (FR3), and a framework region 4 (FR4) of a humanized B-H LC of Table 2; and/or
(b) a heavy chain variable region (VH) comprising:
(i) one, two or all of (e.g., three) a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2) and a heavy chain complementarity determining region 3 (HC CDR3) of a humanized B-H heavy chain (HC) of Table 2; and
(ii) a framework region (FR) having at least 95% identity with one, two, three or all (e.g., four) of a framework region 1 (FR1), a framework region 2 (FR2), a framework region 3 (FR3), and a framework region 4 (FR4) of a humanized B-H HC of Table 2.

### Claim 33 (depends on 32)

The anti-TCRβV antibody molecule of claim 32, which binds to TCRβV12, e.g., TCRβV12-4*01, TCRβV12-3*01, or TCRβV12-5*01, or a variant thereof.

### Claim 34 (depends on 32, 33)

The anti-TCRβV antibody molecule of claim 32 or 33, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(i) a HC CDR1, a HC CDR2 and a HC CDR3 of Antibody B-H listed in Table 2; or
(ii) a LC CDR1, a LC CDR2, and a LC CDR3 of Antibody B-H listed in Table 2.

### Claim 35 (depends on 32, 33, 34)

The anti-TCRβV antibody molecule of any of claims 32-34, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all (e.g., three) of a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11, or an amino acid sequence listed in Table 1.

### Claim 36 (depends on 32, 33, 34, 35)

The anti-TCRβV antibody molecule of any of claims 32-35, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising a heavy chain variable region (VH) comprising one, two or all (e.g., three) of a HC CDR1, a HC CDR2 and a HC CDR3 of a humanized Antibody B-H listed in Table 2.

### Claim 37 (depends on 32, 33, 34, 35, 36)

The anti-TCRβV antibody molecule of any of claims 32-36, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all (e.g., three) of a LC CDR1, a LC CDR2 and a LC CDR3 of a humanized Antibody B-H listed in Table 2.

### Claim 38 (depends on 32, 33, 34, 35, 36, 37)

The anti-TCRβV antibody molecule of any of claims 32-37, wherein the anti-TCRβV antibody molecule comprises:
a VH sequence of a humanized Antibody B-H listed in Table 2, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity to a VH of a humanized Antibody B-H listed in Table 2; and/or
a VL sequence of a humanized Antibody B-H listed in Table 2, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity to a VL of a humanized Antibody B-H listed in Table 2.

### Claim 39 (depends on 32, 33, 34, 35, 36, 37, 38)

The anti-TCRβV antibody molecule of any of claims 32-38, wherein the anti-TCRβV antibody molecule comprises a framework region (FR) having at least 95% identity with one of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H LC of Table 2.

### Claim 40 (depends on 32, 33, 34, 35, 36, 37, 38, 39)

The anti-TCRβV antibody molecule of any of claims 32-39, wherein the anti-TCRβV antibody molecule comprises a framework region (FR) having at least 95% identity with any two of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H LC of Table 2.

### Claim 41 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40)

The anti-TCRβV antibody molecule of any of claims 32-40, wherein the anti-TCRβV antibody molecule comprises a framework region (FR) having at least 95% identity with any three of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H LC of Table 2.

### Claim 42 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41)

The anti-TCRβV antibody molecule of any of claims 32-41, wherein the anti-TCRβV antibody molecule comprises a framework region (FR) having at least 95% identity with all of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H LC of Table 2.

### Claim 43 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)

The anti-TCRβV antibody molecule of any of claims 32-42, wherein the anti-TCRβV antibody molecule comprises a framework region (FR) having at least 95% identity with one of:
a FR1, a FR2, a FR3, and a FR4 of a humanized B-H HC of Table 2.

### Claim 44 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)

The anti-TCRβV antibody molecule of any of claims 32-42, wherein the anti-TCRβV antibody molecule comprises a framework region (FR) having at least 95% identity with any two of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H HC of Table 2.

### Claim 45 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)

The anti-TCRβV antibody molecule of any of claims 32-42, wherein the anti-TCRβV antibody molecule comprises a framework region (FR) having at least 95% identity with any three of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H HC of Table 2.

### Claim 46 (depends on 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)

The anti-TCRβV antibody molecule of any of claims 32-42, wherein the anti-TCRβV antibody molecule comprises a framework region (FR) having at least 95% identity with all of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H HC of Table 2.

### Claim 47 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46)

The anti-TCRβV antibody molecule of any of claims 17 to 46, wherein binding of the anti-TCRβV antibody molecule to the TCRβV region results in a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCRβV region (“a non-TCRβV-binding T cell engager”).

### Claim 48 (depends on 47)

The anti-TCRβV antibody molecule of claim 47, wherein the non-TCRβV-binding T cell engager comprises an antibody that binds to a CD3 molecule (e.g., CD3 epsilon (CD3e) molecule); or a TCR alpha (TCRα) molecule.

### Claim 49 (depends on 47, 48)

The anti-TCRβV antibody molecule of claim 47 or 48, wherein the cytokine profile of the first moiety comprises, one, two, three, four, five, six, seven, or all of the following:
(i) increased level, e.g., expression level, and/or activity of IL-2;
(ii) reduced level, e.g., expression level, and/or activity of IL-1β;
(iii) reduced level, e.g., expression level, and/or activity of IL-6;
(iv) reduced level, e.g., expression level, and/or activity of TNFα;
(v) reduced level, e.g., expression level, and/or activity of IL-10;
(vi) a delay, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more hours delay, in increased level, e.g., expression level, and/or activity of IL-2;
(vii) a delay, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 hours delay, in increased level, e.g., expression level, and/or activity of IFNg; or
(viii) increased level, e.g., expression level, and/or activity of IL-15,
e.g., wherein (i)-(vii) are relative to the cytokine profile of the non-TCRβV-binding T cell engager.

### Claim 50 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49)

The anti-TCRβV antibody molecule of any of claims 17 to 49, wherein binding of the anti-TCRβV antibody molecule to the TCRβV region results in reduced cytokine storm, e.g., reduced cytokine release syndrome (CRS), as measured by an assay of Example 3, e.g., relative to the cytokine storm induced by the non-TCRβV-binding T cell engager.

### Claim 51 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50)

The anti-TCRβV antibody molecule of any of claims 17 to 50, wherein binding of the anti-TCRβV antibody molecule to the TCRβV region results in one, two, three or all of:
(ix) reduced T cell proliferation kinetics;
(x) cell killing, e.g., target cell killing, e.g. cancer cell killing, e.g., as measured by an assay of Example 4;
(xi) increased Natural Killer (NK) cell proliferation, e.g., expansion; or
(xii) expansion, e.g., at least about 1.1-10 fold expansion (e.g., at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion), of a population of memory T cells,
e.g., relative to the non-TCRβV-binding T cell engager.

### Claim 52 (depends on 51)

The anti-TCRβV antibody molecule of claim 51, wherein the population of memory T cells comprises T effector memory (TEM) cells, e.g., TEM cells expressing CD45RA (TEMRA) cells.

### Claim 53

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein binding of the anti-TCRβV antibody molecule to a TCRβV region results in a reduction of at least 2, 5, 10, 20, 50, 100, or 200 fold, or at least 2-200 fold (e.g., 5-150, 10-100, 20-50 fold) in the expression level and or activity of IL-1(3 as measured by an assay of Example 3.

### Claim 54

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein binding of the anti-TCRβV antibody molecule to a TCRβV region results in a reduction of at least 2, 5, 10, 20, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 fold, or at least 2-1000 fold (e.g., 5-900, 10-800, 20-700, 50-600, 100-500, or 200-400 fold) in the expression level and or activity of IL-6 as measured by an assay of Example 3.

### Claim 55

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, binding of the anti-TCRβV antibody molecule to a TCRβV region results in a reduction of at least 2, 5, 10, 20, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or 2000 fold, or at least 2-2000 fold (e.g., 5-1000, 10-900, 20-800, 50-700, 100-600, 200-500, or 300-400 fold) in the expression level and or activity of TNFα as measured by an assay of Example 3.

### Claim 56

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein binding of the anti-TCRβV antibody molecule to a TCRβV region results in an increase of at least 2, 5, 10, 20, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or 2000 fold, or at least 2-2000 fold (e.g., 5-1000, 10-900, 20-800, 50-700, 100-600, 200-500, or 300-400 fold) in the expression level and or activity of IL-2 as measured by an assay of Example 3.

### Claim 57

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising a single chain Fv (scFv) or a Fab.

### Claim 58

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule binds to a conformational or a linear epitope on the T cell.

### Claim 59

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule is a full antibody (e.g., an antibody that includes at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains), or an antigen-binding fragment (e.g., a Fab, F(ab′)2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, or a camelid antibody).

### Claim 60

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises one or more heavy chain constant regions chosen from IgG1, IgG2, IgG3, IgGA1, IgGA2, IgG4, IgJ, IgM, IgD, or IgE, or a fragment thereof, e.g., as described in Table 3.

### Claim 61

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises a heavy chain constant region of an IgM or a fragment thereof, optionally wherein the IgM heavy chain constant region comprises the sequence of SEQ ID NO: 73, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.

### Claim 62

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises a heavy chain constant region of an IgJ or a fragment thereof, optionally wherein the IgJ heavy chain constant region comprises the sequence of SEQ ID NO: 76 or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.

### Claim 63

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises a heavy chain constant region of an IgGA1, or a fragment thereof, optionally wherein the IgGA1 heavy chain constant region comprises the sequence of SEQ ID NO: 74, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.

### Claim 64

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises a heavy chain constant region of an IgGA2, or a fragment thereof, optionally wherein the IgGA2 heavy chain constant region comprises a sequence listed in Table 3, e.g., SEQ ID NO: 75, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.

### Claim 65

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises a light chain constant region chosen from the light chain constant regions of kappa or lambda, or a fragment thereof, e.g., as described in Table 3.

### Claim 66

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises a light chain constant region of a kappa chain, or a fragment thereof, optionally wherein the kappa chain constant region comprises the sequence of SEQ ID NO: 39, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.

### Claim 67

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises:
(i) one or more heavy chain constant regions comprising a heavy chain constant region chosen from IgG1, IgG2, IgG3, IgGA1, IgGA2, IgG4, IgJ, IgM, IgD, or IgE, or a fragment thereof, e.g., as described in Table 3; and
(ii) a light chain constant region comprising a light chain constant region chosen from the light chain constant regions of kappa or lambda, or a fragment thereof, e.g., as described in Table 3.

### Claim 68

The multispecific molecule or the anti-TCRβV antibody molecule of any of the preceding claims, wherein the anti-TCRβV antibody molecule comprises:
(i) a heavy chain constant region comprising:
(a) an IgM heavy chain constant region or a fragment thereof, comprising the sequence of SEQ ID NO: 73, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto;
(b) an IgGA1 heavy chain constant region or a fragment thereof, comprising the sequence of SEQ ID NO: 74, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto; or
(c) an IgGA2 heavy chain constant region or a fragment thereof, comprising the sequence of SEQ ID NO: 75, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto; and
(ii) a light chain constant region comprising a kappa chain constant region comprising the sequence of SEQ ID NO: 39, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto,
optionally wherein, the anti-TCRβV antibody molecule further comprises an IgJ heavy chain constant region or a fragment thereof, wherein the IgJ heavy chain constant region comprises the sequence of SEQ ID NO: 76 or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.

### Claim 69 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68)

The multispecific molecule of any one of claim 1-16 or 53-68, wherein the second moiety is a tumor-targeting moiety.

### Claim 70 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68)

The multispecific molecule of any one of claim 1-16 or 53-68, wherein the second moiety is a cytokine molecule.

### Claim 71 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68)

The multispecific molecule of any one of claim 1-16 or 53-68, wherein the second moiety is a stromal modifying moiety.

### Claim 72 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68)

The multispecific molecule of any one of claim 1-16 or 53-68, wherein the second moiety is an anti-TCRβV antibody molecule other than the first moiety.

### Claim 73 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72)

The multispecific molecule of any one of claim 1-16 or 53-72, wherein the first and/or second moiety binds to and activates an immune cell, e.g., an effector cell.

### Claim 74 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72)

The multispecific molecule of any one of claim 1-16 or 53-72, wherein the first and/or second moiety binds to, but does not activate an immune cell, e.g., an effector cell.

### Claim 75 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74)

The multispecific molecule of any one of claim 1-16 or 53-74, wherein the second moiety is chosen from an NK cell engager, a T cell engager other than an anti-TCRβV antibody molecule, a B cell engager, a dendritic cell engager, or a macrophage cell engager, or a combination thereof.

### Claim 76 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69)

The multispecific molecule of any one of claim 1-16 or 53-69, wherein the tumor-targeting moiety comprises an antibody molecule (e.g., Fab or scFv), a receptor molecule (e.g., a receptor, a receptor fragment or functional variant thereof), or a ligand molecule (e.g., a ligand, a ligand fragment or functional variant thereof), or a combination thereof, that binds to a cancer antigen.

### Claim 77 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 76)

The multispecific molecule of any one of claim 1-16, 53-69 or 76, wherein the tumor-targeting moiety binds to a cancer antigen present on a cancer, e.g., a hematological cancer, a solid tumor, a metastatic cancer, soft tissue tumor, metastatic lesion, or a combination thereof.

### Claim 78 (depends on 77)

The multispecific molecule of claim 77, wherein the cancer antigen is a tumor antigen or stromal antigen, or a hematological antigen.

### Claim 79 (depends on 77, 78)

The multispecific molecule of claim 77 or 78, wherein the cancer antigen is chosen from: BCMA, FcRH5, PDL1, CD47, gangloside 2 (GD2), prostate stem cell antigen (PSCA), prostate specific membrane antigen (PMSA), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), Ron Kinase, c-Met, Immature laminin receptor, TAG-72, BING-4, Calcium-activated chloride channel 2, Cyclin-B1, 9D7, Ep-CAM, EphA3, Her2/neu, Telomerase, SAP-1, Survivin, NY-ESO-1/LAGE-1, PRAME, SSX-2, Melan-A/MART-1, Gp100/pmel17, Tyrosinase, TRP-1/-2, MC1R, β-catenin, BRCA1/2, CDK4, CML66, Fibronectin, p53, Ras, TGF-B receptor, AFP, ETA, MAGE, MUC-1, CA-125, BAGE, GAGE, NY-E50-1, β-catenin, CDK4, CDCl27, a actinin-4, TRP1/gp75, TRP2, gp100, Melan-A/MART1, gangliosides, WT1, EphA3, Epidermal growth factor receptor (EGFR), MART-2, MART-1, MUC1, MUC2, MUM1, MUM2, MUM3, NA88-1, NPM, 0A1, OGT, RCC, RUI1, RUI2, SAGE, TRG, TRP1, TSTA, Folate receptor alpha, L1-CAM, CAIX, gpA33, GD3, GM2, VEGFR, Intergrins (Integrin alphaVbeta3, Integrin alpha5Beta1), Carbohydrates (Le), IGF1R, EPHA3, TRAILR1, TRAILR2, RANKL, (FAP), TGF-beta, hyaluronic acid, collagen, e.g., collagen IV, tenascin C, or tenascin W.

### Claim 80 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 76, 77, 78, 79)

The multispecific molecule of any one of claim 1-16, 53-69 or 76-79, wherein the tumor-targeting moiety is a BCMA targeting moiety or a FcRH5 targeting moiety.

### Claim 81 (depends on 77, 78, 79, 80)

The multispecific molecule of any one of claims 77-80, wherein the cancer is a solid tumor including but not limited to: pancreatic (e.g., pancreatic adenocarcinoma) cancer, breast cancer, colorectal cancer, lung cancer (e.g., small or non-small cell lung cancer), skin cancer, ovarian cancer, or liver cancer.

### Claim 82 (depends on 77, 78, 79, 80)

The multispecific molecule of any one of claims 77-80, wherein the cancer is a hematological cancer including, but not limited to: a B-cell or T cell malignancy, e.g., Hodgkin's lymphoma, Non-Hodgkin's lymphoma (e.g., B cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia), acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, and acute lymphocytic leukemia.

### Claim 83 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 70)

The multispecific molecule of any one of claim 1-16, 53-68 or 70, wherein the cytokine molecule is chosen from interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12), interleukin-15 (IL-15), interleukin-18 (IL-18), interleukin-21 (IL-21), or interferon gamma, or a fragment, variant or combination thereof.

### Claim 84 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 70, 83)

The multispecific molecule of any one of claim 1-16, 53-68, 70 or 83, wherein the cytokine molecule is a monomer or a dimer.

### Claim 85 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 70, 83, 84)

The multispecific molecule of any one of claim 1-16, 53-68, 70 or 83-84 wherein the cytokine molecule further comprises a receptor dimerizing domain, e.g., an IL15Ralpha dimerizing domain.

### Claim 86 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 70, 83, 84, 85)

The multispecific molecule of any one of claim 1-16, 53-68, 70 or 83-85, wherein the cytokine molecule (e.g., IL-15) and the receptor dimerizing domain (e.g., an IL15Ralpha dimerizing domain) are not covalently linked, e.g., are non-covalently associated.

### Claim 87 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

The multispecific molecule of any one of claim 1-16, or 53-86, further comprising an immunoglobulin constant region (e.g., Fc region) chosen from the heavy chain constant regions of IgG1, IgG2, IgG3, IgGA1, IgGA2, IgG4, IgJ, IgM, IgD, or IgE, or a fragment thereof, optionally wherein, the heavy chain constant region comprises the heavy chain constant region of human IgG1, IgG2 or IgG4.

### Claim 88 (depends on 87)

The multispecific molecule of claim 87, wherein the immunoglobulin constant region (e.g., an Fc region) is linked, e.g., covalently linked to, one or more of tumor-targeting moiety, the cytokine molecule, or the stromal modifying moiety.

### Claim 89 (depends on 87, 88)

The multispecific molecule of claim 87 or 88, wherein an interface of a first and second immunoglobulin chain constant regions (e.g., Fc region) is altered, e.g., mutated, to increase or decrease dimerization, e.g., relative to a non-engineered interface.

### Claim 90 (depends on 89)

The multispecific molecule of claim 89, wherein the dimerization of the immunoglobulin chain constant region (e.g., Fc region) is enhanced by providing an Fc interface of a first and a second Fc region with one or more of: a paired cavity-protuberance (“knob-in-a hole”), an electrostatic interaction, or a strand-exchange, such that a greater ratio of heteromultimer:homomultimer forms, e.g., relative to a non-engineered interface.

### Claim 91 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

The multispecific molecule of any one of claim 1-16, or 53-90, further comprising a linker, e.g., a linker described herein, optionally wherein the linker is selected from: a cleavable linker, a non-cleavable linker, a peptide linker, a flexible linker, a rigid linker, a helical linker, or a non-helical linker.

### Claim 92 (depends on 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53)

An isolated nucleic acid molecule comprising a nucleotide sequence encoding the anti-TCRβV antibody molecule of any of claims 17-53, or a nucleotide sequence having at least 75%, 80%, 85%, 90%, 95%, or 99% identity thereto.

### Claim 93 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

An isolated nucleic acid molecule comprising a nucleotide sequence encoding the multispecific molecule of any of claim 1-16, or 53-91, or a nucleotide sequence having at least 75%, 80%, 85%, 90%, 95%, or 99% identity thereto.

### Claim 94 (depends on 92, 93)

A vector, e.g., an expression vector, comprising one or more of the nucleic acid molecules of any one of claim 92 or 93.

### Claim 95 (depends on 92, 93, 94)

A cell, e.g., host cell, comprising the nucleic acid molecule of any of claim 92 or 93, or the vector of claim 94.

### Claim 96 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 95)

A method of making, e.g., producing or manufacturing, the anti-TCRβV antibody molecule of any of claims 17-53, or the multispecific molecule of any of claim 1-16, or 53-91, comprising culturing the host cell of claim 95, under suitable conditions, e.g., conditions suitable expression of the anti-TCRβV antibody molecule or the multispecific molecule.

### Claim 97 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53)

A pharmaceutical composition comprising the anti-TCRβV antibody molecule of any of claims 17-53, or the multispecific molecule of any of claim 1-16, or 53-91, and a pharmaceutically acceptable carrier, excipient, or stabilizer.

### Claim 98

A method of modulating, e.g., enhancing, an immune response in a subject comprising administering to the subject an effective amount of an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”).

### Claim 99 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A method of modulating, e.g., enhancing, an immune response in a subject comprising administering to the subject an effective amount of the multispecific molecule of any of claim 1-16, or 53-91.

### Claim 100 (depends on 98, 99)

The method of claim 98 or 99, wherein the method comprises expanding, e.g., increasing the number of, an immune cell population in the subject.

### Claim 101

A method of expanding, e.g., increasing the number of, an immune cell population comprising, contacting the immune cell population with an effective amount of an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”).

### Claim 102 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A method of expanding, e.g., increasing the number of, an immune cell population comprising, contacting the immune cell population with an effective amount of the multispecific molecule of any of claim 1-16, or 53-91.

### Claim 103 (depends on 100, 101, 102)

The method of any of claims 100 to 102, wherein the expansion occurs in vivo or ex vivo (e.g., in vitro).

### Claim 104 (depends on 100, 101, 102, 103)

The method of any of claims 100 to 103, wherein the immune cell population comprises a TCRβV expressing cell, e.g., a TCRβV+ cell.

### Claim 105 (depends on 104)

The method of claim 104, wherein the TCRβV expressing cell is a T cell, e.g., a CD8+ T cell, a CD3+ T cell or a CD4+ T cell.

### Claim 106 (depends on 100, 101, 102, 103, 104, 105)

The method of any of claims 100 to 105, wherein the immune cell population comprises a T cell (e.g., a CD4 T cell, a CD8 T cell, (e.g., an effector T cell or a memory T cell (e.g., a memory effector T cell (e.g., TEM cell, e.g., TEMRA cell), or a tumor infiltrating lymphocyte (TIL).

### Claim 107 (depends on 100, 101, 102, 103, 104, 105, 106)

The method of any of claims 100-106, wherein the immune cell population comprises a T cell, a Natural Killer cell, a B cell, or a myeloid cell.

### Claim 108 (depends on 100, 101, 102, 103, 104, 105, 106, 107)

The method of any of claims 100-107, wherein the immune cell population is obtained from a healthy subject.

### Claim 109 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108)

The method of any of claims 100-108, wherein the immune cell population is obtained from a subject (e.g., from an apheresis sample from the subject) having a disease, e.g., a cancer, e.g., as described herein, optionally wherein the immune cell population comprises a tumor infiltrating lymphocyte (TIL).

### Claim 110 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109)

The method of any of claims 100-109, wherein the method results in an expansion of at least 1.1-10 fold (e.g., at least 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion).

### Claim 111 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110)

The method of any of claims 100-110, further comprising contacting the population of cells with an agent that promotes, e.g., increases, immune cell expansion.

### Claim 112 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111)

The method of any of claims 100-111, further comprising contacting the population of cells with an immune checkpoint inhibitor, e.g., a PD-1 inhibitor.

### Claim 113 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112)

The method of any of claims 100-112, further comprising contacting the population of cells with a 4-1BB (CD127) agonist, e.g., an anti-4-1BB antibody.

### Claim 114 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113)

The method of any of claims 100-113, further comprising contacting the population of cells with a non-dividing population of cells, e.g., feeder cells, e.g., irradiated allogenic human PBMCs.

### Claim 115 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114)

The method of any of claims 100-114, wherein the population of cells is expanded in an appropriate media (e.g., media described herein) that includes one or more cytokines, e.g., IL-2, IL-7, IL-15, or a combination thereof.

### Claim 116 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115)

The method of any of claims 100-115, wherein the population of cells is expanded for a period of at least about 4 hours, 6 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, or 22 hours, or for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 days, or for at least about 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks or 8 weeks.

### Claim 117 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116)

The method of method of any of claims 100-116, wherein expansion of the population of immune cells, is compared to expansion of a similar population of cells with an antibody that binds to: a CD3 molecule, e.g., CD3 epsilon (CD3e) molecule; or a TCR alpha (TCRα) molecule.

### Claim 118 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117)

The method of claim of any of claims 100-117, wherein expansion of the population of immune cells, is compared to expansion of a similar population of cells not contacted with the anti-TCRβV antibody molecule, or multispecific molecule comprising the anti-TCRβV antibody molecule.

### Claim 119 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118)

The method of claim of any of claims 100-118, wherein expansion of the population of memory effector T cells, e.g., TEM cells, e.g., TEMRA cells, is compared to expansion of a similar population of cells with an antibody that binds to: a CD3 molecule, e.g., CD3 epsilon (CD3e) molecule; or a TCR alpha (TCRα) molecule.

### Claim 120 (depends on 119)

The method of claim of claim 119, wherein the population of expanded T effector memory cells comprises cells which:
(i) have a detectable level of CD45RA, e.g., express or re-express CD45RA;
(ii) have low or no expression of CCR7; and/or
(iii) have a detectable level of CD95, e.g., express CD95,
e.g., a population of CD45RA+, CCR7−, CD95+ T cells, optionally wherein the T cells comprise CD3+, CD4+ or CD8+ T cells.

### Claim 121 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120)

The method of any of claims 100-120, wherein the method results in expansion of, e.g., selective or preferential expansion of, T cells expressing a T cell receptor (TCR) comprising a TCR alpha and/or TCR beta molecule, e.g., TCR alpha-beta T cells (αβ T cells).

### Claim 122 (depends on 121)

The method of claim 121, wherein the method results in expansion of αβT cells over expansion of T cells expressing a TCR comprising a TCR gamma and/or TCR delta molecule, e.g., TCR gamma-delta T cells (γδ T cells).

### Claim 123

A method of treating a disease, e.g., cancer, in a subject comprising administering to the subject an effective amount of an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”), thereby treating the cancer.

### Claim 124

A composition comprising an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”), for use in treating a disease, e.g., cancer, in a subject.

### Claim 125

A composition comprising an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”), for use in the manufacture of a medicament for treating a disease, e.g., cancer, in a subject.

### Claim 126 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A method of treating a disease, e.g., cancer, in a subject comprising administering to the subject an effective amount of the multispecific molecule of any of claim 1-16, or 53-91, thereby treating the cancer.

### Claim 127 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A composition comprising the multispecific molecule of any of claim 1-16, or 53-91, for use in treating a disease, e.g., cancer, in a subject.

### Claim 128 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A composition comprising the multispecific molecule of any of claim 1-16, or 53-91, for use in the manufacture of a medicament for treating a disease, e.g., cancer, in a subject.

### Claim 129

A method of treating, e.g., preventing or reducing, cytokine release syndrome (CRS) and/or neurotoxicity (NT) in a subject, e.g., CRS and/or NT associated with a treatment, e.g., a previously administered treatment, comprising administering to the subject an effective amount of an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”), thereby preventing CRS and/or NT in the subject.

### Claim 130 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A method of treating, e.g., preventing or reducing, cytokine release syndrome (CRS) and/or neurotoxicity (NT) in a subject, e.g., CRS and/or NT associated with a treatment, e.g., a previously administered treatment, comprising administering to the subject an effective amount the multispecific molecule of any of claim 1-16, or 53-91, thereby preventing CRS and/or NT in the subject.

### Claim 131

A method of targeting a therapy, e.g., treatment, to a T cell in a subject having a disease, e.g., cancer, comprising administering an effective amount of:
(i) an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”); and
(ii) the therapy, e.g., a tumor targeting therapy (e.g., an antibody that binds to a cancer antigen), e.g., as described herein,
thereby targeting the therapy to the T cell in the subject.

### Claim 132 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A method of targeting a therapy, e.g., treatment, to a T cell in a subject having a disease, e.g., cancer, comprising administering an effective amount of:
(i) the multispecific molecule of any of claim 1-16, or 53-91; and
(ii) the therapy, e.g., a tumor targeting therapy (e.g., an antibody that binds to a cancer antigen), e.g., as described herein,
thereby targeting the therapy to the T cell in the subject.

### Claim 133 (depends on 131, 132)

The method of claim 131 or 132, wherein the method results in: reduced cytokine release syndrome (CRS) (e.g., lesser duration of CRS or no CRS), or a reduced severity of CRS (e.g., absence of severe CRS, e.g., CRS grade 4 or 5) compared to administration of (ii) alone.

### Claim 134 (depends on 131, 132, 133)

The method of any one of claims 131-133, wherein the anti-TCRβV antibody or the multispecific molecule is administered concurrently with or after the administration of the treatment associated with CRS.

### Claim 135

A method of treating a subject having a cancer, the method comprising:
acquiring a value of the status of a TCRβV subfamily for the subject, wherein said value comprises a measure of the presence of, e.g., level or activity of, a TCRβV molecule in a sample from the subject, and
administering an effective amount of an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”); to the subject,
thereby treating the subject.

### Claim 136 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A method of treating a subject having a cancer, the method comprising:
acquiring a value of the status of a TCRβV subfamily for the subject, wherein said value comprises a measure of the presence of, e.g., level or activity of, a TCRβV molecule in a sample from the subject, and
administering an effective amount of the multispecific molecule of any of claim 1-16, or 53-91 to the subject,
thereby treating the subject.

### Claim 137

A method of treating a subject having a cancer, the method comprising administering an effective amount of an antibody molecule which binds (e.g., specifically binds) to a T cell receptor beta variable region (TCRβV) (“anti-TCRβV antibody molecule”) to the subject, wherein the subject has a higher, e.g., increased, level or activity of one or more TCRβV subfamilies, e.g., as described herein, compared to a reference level or activity of one or more TCRβV subfamilies, e.g., in a healthy subject, e.g., a subject not having a cancer.

### Claim 138 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A method of treating a subject having a cancer, the method comprising administering an effective amount of the multispecific molecule of any of claim 1-16, or 53-91 to the subject, wherein the subject has a higher, e.g., increased, level or activity of one or more TCRβV subfamilies, e.g., as described herein, compared to a reference level or activity of one or more TCRβV subfamilies, e.g., in a healthy subject, e.g., a subject not having a cancer.

### Claim 139

A method of expanding a population of immune effector cells from a subject having a cancer, the method comprising:
(i) isolating a biological sample comprising a population of immune effector cells from the subject; e.g., a peripheral blood sample, biopsy sample, or bone marrow sample;
(ii) acquiring a value of the status of one or more TCRβV subfamilies for the subject, e.g., in the biological sample from the subject, wherein said value comprises a measure of the presence of, e.g., level or activity of, a TCRβV subfamily in a sample from the subject compared to a reference value, e.g., a sample from a health subject, wherein a value that is higher, e.g., increased, in the subject relative to the reference, e.g., healthy subject, is indicative of the presence of cancer in the subject, and
(iii) contacting the biological sample comprising a population of immune effector cells with an anti-TCRβV antibody molecule, e.g., as described herein.

### Claim 140 (depends on 139)

The method of claim 139, further comprising administering the population of immune effector cells contacted with the anti-TCRβV antibody molecule to the subject.

### Claim 141 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

A method of expanding a population of immune effector cells from a subject having a cancer, the method comprising:
(i) isolating a biological sample comprising a population of immune effector cells from the subject; e.g., a peripheral blood sample, biopsy sample, or bone marrow sample;
(ii) acquiring a value of the status of one or more TCRβV subfamilies for the subject, e.g., in the biological sample from the subject, wherein said value comprises a measure of the presence of, e.g., level or activity of, a TCRβV subfamily in a sample from the subject compared to a reference value, e.g., a sample from a health subject, wherein a value that is higher, e.g., increased, in the subject relative to the reference, e.g., healthy subject, is indicative of the presence of cancer in the subject, and
(iii) contacting the biological sample comprising a population of immune effector cells with the multispecific molecule of any of claim 1-16, or 53-91.

### Claim 142 (depends on 141)

The method of claim 141, further comprising administering the population of immune effector cells contacted with the multispecific molecule to the subject.

### Claim 143 (depends on 139, 140, 141, 142)

The method of any one of claims 139-142, comprising measuring T cell function (e.g., cytotoxic activity, cytokine secretion, or degranulation) in the population of immune effector cells, e.g., compared to a reference population, e.g., an otherwise similar population not contacted with the anti-TCRβV antibody molecule or a population of immune effector cells obtained from a healthy subject (e.g., a subject that does not have a cancer).

### Claim 144 (depends on 139, 140, 141, 142, 143)

The method of any one of claims 139-143, wherein the biological sample comprising the population of immune effector cells is contacted with an anti-TCRβV antibody molecule or a multispecific molecule that binds to the one or more TCRβV subfamilies (e.g., the same TCRβV subfamily) identified as being higher, e.g., increased, in the biological sample.

### Claim 145 (depends on 139, 140, 141, 142, 143, 144)

The method of any one of claims 139-144, wherein the biological sample comprising the population of immune effector cells is contacted with an anti-TCRβV antibody molecule or a multispecific molecule that does not bind to the one or more TCRβV subfamilies (e.g., a different TCRβV subfamily) identified as being higher, e.g., increased, in the biological sample.

### Claim 146 (depends on 139, 140, 141, 142, 143, 144, 145)

The method of any one of claims 139-145, wherein the cancer is a solid tumor including but not limited to: melanoma, pancreatic (e.g., pancreatic adenocarcinoma) cancer, breast cancer, colorectal cancer (CRC), lung cancer (e.g., small or non-small cell lung cancer), skin cancer, ovarian cancer, or liver cancer.

### Claim 147 (depends on 139, 140, 141, 142, 143, 144, 145)

The method of any one of claims 139-145, wherein the cancer is a hematological cancer including, but not limited to: a B-cell or T cell malignancy, e.g., Hodgkin's lymphoma, Non-Hodgkin's lymphoma (e.g., B cell lymphoma, diffuse large B cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia), acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, and acute lymphocytic leukemia.

### Claim 148 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147)

The method of any one of claims 139-147, wherein the cancer is B-CLL and the TCRβV molecule comprises:
(i) TCRβV6 subfamily comprising, e.g., TCRβV6-4*01, TCRβV6-4*02, TCRβV6-9*01, TCRβV6-8*01, TCRβV6-5*01, TCRβV6-6*02, TCRβV6-6*01, TCRβV6-2*01, TCRβV6-3*01 or TCRβV6-1*01;
(ii) TCRβV5 subfamily comprising TCRβV5-6*01, TCRβV5-4*01, or TCRβV5-8*01;
(iii) TCRβV3 subfamily comprising TCRβV3-1*01;
(iv) TCRβV2 subfamily comprising TCRβV2*01; or
(v) TCRβV19 subfamily comprising TCRβV19*01, or TCRβV19*02.

### Claim 149 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147)

The method of any one of claims 139-147, wherein the cancer is melanoma and the TCRβV molecule comprises the TCRβV6 subfamily comprising, e.g., TCRβV6-4*01, TCRβV6-4*02, TCRβV6-9*01, TCRβV6-8*01, TCRβV6-5*01, TCRβV6-6*02, TCRβV6-6*01, TCRβV6-2*01, TCRβV6-3*01 or TCRβV6-1*01.

### Claim 150 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147)

The method of any one of claims 139-147, wherein the cancer is DLBCL and the TCRβV molecule comprises:
(i) TCRβV13 subfamily comprising TCRβV13*01;
(ii) TCRβV3 subfamily comprising TCRβV3-1*01; or
(iii) TCRβV23 subfamily.

### Claim 151 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147)

The method of any one of claims 139-147, wherein the cancer is CRC and the TCRβV molecule comprises:
(i) TCRβV19 subfamily comprising TCRβV19*01, or TCRβV19*02
(ii) TCRβV12 subfamily comprising TCRβV12-4*01, TCRβV12-3*01, or TCRβV12-5*01
(iii) TCRβV16 subfamily comprising TCRβV16*01; or
(iv) TCRβV21 subfamily.

### Claim 152 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151)

The method of any one of claims 139-151, wherein:
the tumor comprises an antigen, e.g., a tumor antigen, e.g., a tumor associated antigen or a neoantigen; and/or
the one or more TCRβV subfamilies recognize, e.g., bind to, the tumor antigen.

### Claim 153 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152)

The method of any one of claims 139-152, wherein the sample comprises a blood sample, e.g., a peripheral blood sample, a biopsy, e.g., a tumor biopsy, or a bone marrow sample.

### Claim 154 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152)

The method of any one of claims 139-152, wherein the sample comprises a biological sample comprising immune cells, e.g., TCRBV expressing cells (e.g., TCRBV+ cells), T cells, or NK cells.

### Claim 155 (depends on 154)

The method of claim 154, wherein the T cells comprise a CD4 T cell, a CD8 T cell, (e.g., an effector T cell or a memory T cell (e.g., a memory effector T cell (e.g., TEM cell, e.g., TEMRA cell), or a tumor infiltrating lymphocyte (TIL).

### Claim 156 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155)

The method of any of claims 139-155, wherein the method results in an expansion, e.g., in vivo or ex vivo expansion, of at least 1.1-1000 fold, e.g., 1.1-10, 10-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, or 900-1000 fold expansion of an immune effector cell population comprising a TCRVB expressing immune effector cell, e.g., T cell.

### Claim 157 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156)

The method of any of claims 139-156, wherein the population of cells is expanded in an appropriate media (e.g., media described herein) that includes one or more cytokines, e.g., IL-2, IL-7, IL-15, or a combination thereof.

### Claim 158 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157)

The method of any of claims 139-157, wherein the population of cells is expanded for a period of at least about 4 hours, 6 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, or 22 hours, or for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or 21 days, or for at least about 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks or 8 weeks.

### Claim 159 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158)

The method of any of claims 139-158, wherein expansion of the population of immune cells, is compared to expansion of a similar population of cells with an antibody that binds to: a CD3 molecule, e.g., CD3 epsilon (CD3e) molecule; or a TCR alpha (TCRα) molecule.

### Claim 160 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159)

The method of any of claims 139-159, expansion of the population of immune cells, is compared to expansion of a similar population of cells not contacted with the anti-TCRβV antibody molecule.

### Claim 161 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160)

The method of any of claims 139-160, wherein expansion of the population of memory effector T cells, e.g., TEM cells, e.g., TEMRA cells, is compared to expansion of a similar population of cells with an antibody that binds to: a CD3 molecule, e.g., CD3 epsilon (CD3e) molecule; or a TCR alpha (TCRα) molecule.

### Claim 162 (depends on 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161)

The method of any of claims 133-161, wherein the population of expanded T effector memory cells comprises cells which:
(i) have a detectable level of CD45RA, e.g., express or re-express CD45RA;
(ii) have low or no expression of CCR7; and/or
(iii) have a detectable level of CD95, e.g., express CD95,
e.g., a population of CD45RA+, CCR7−, CD95+ T cells, optionally wherein the T cells comprise CD3+, CD4+ or CD8+ T cells.

### Claim 163 (depends on 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162)

The method of any of claims 139-162, wherein the method results in expansion of, e.g., selective or preferential expansion of, T cells expressing a T cell receptor (TCR) comprising a TCR alpha and/or TCR beta molecule, e.g., TCR alpha-beta T cells (αβ T cells).

### Claim 164 (depends on 163)

The method of claim 163, wherein the method results in expansion of αβT cells over expansion of T cells expressing a TCR comprising a TCR gamma and/or TCR delta molecule, e.g., TCR gamma-delta T cells (γδ T cells).

### Claim 165 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164)

The method, or composition for use of any one of claims 98-164, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all of a LC CDR1, a LC CDR2 and a LC CDR3 of a VL disclosed in Tables 1, 2, 10, 11 or 12, e.g., SEQ ID NO: 2, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 16, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO:30

### Claim 166 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165)

The method, or composition for use of any one of claims 98-165, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising a heavy chain variable region (VH) comprising one, two or all of a HC CDR1, a HC CDR2 and a HC CDR3 of a VH disclosed in Tables 1, 2, 10, 11 or 12, e.g., SEQ ID NO:1, SEQ ID NO: 9, SEQ ID NO: 15, SEQ ID NO: 23, SEQ ID NO: 24 or SEQ ID NO: 25.

### Claim 167 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166)

The method, or composition for use of any one of claims 98-166, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
(i) a VL comprising: a LC CDR1 amino acid sequence of SEQ ID NO: 20 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), a LC CDR2 amino acid sequence of SEQ ID NO:21 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), and/or a LC CDR3 amino acid sequence of SEQ ID NO:22 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof); and/or
(ii) a VH comprising: a HC CDR1 amino acid sequence of SEQ ID NO: 17 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), a HC CDR2 amino acid sequence of SEQ ID NO:18 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), and/or a HC CDR3 amino acid sequence of SEQ ID NO:19 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof).

### Claim 168 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167)

The method, or composition for use of any one of claims 98-167, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
a variable heavy chain (VH) of SEQ ID NO: 23, SEQ ID NO: 24 or SEQ ID NO: 25, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto; and/or
a variable light chain (VL) of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO:30, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto.

### Claim 169 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168)

The method, or composition for use of any one of claims 98-168, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising
(i) a VL comprising: a LC CDR1 amino acid sequence of SEQ ID NO: 6 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), a LC CDR2 amino acid sequence of SEQ ID NO:7 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), and/or a LC CDR3 amino acid sequence of SEQ ID NO: 8 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof); and/or
(ii) a VH comprising: a HC CDR1 amino acid sequence of SEQ ID NO: 3 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), a HC CDR2 amino acid sequence of SEQ ID NO:4 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof), and/or a HC CDR3 amino acid sequence of SEQ ID NO:5 (or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, e.g., substitutions, additions or deletions thereof).

### Claim 170 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169)

The method, or composition for use of any one of claims 98-169, wherein the anti-TCRβV antibody molecule comprises an antigen binding domain comprising:
a variable heavy chain (VH) of SEQ ID NO: 1 or SEQ ID NO: 9, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto; and/or
a variable light chain (VL) of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO:11, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto.

### Claim 171 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170)

The method, or composition for use of any one of claims 98-170, wherein the anti-TCRβV antibody molecule comprises a light chain comprising a framework region, e.g., framework region 1 (FR1), comprising one, two or all (e.g., three) of:
(i) an Aspartic Acid at position 1, e.g., a substitution at position 1 according to Kabat numbering, e.g., a Alanine to Aspartic Acid substitution; or
(ii) an Asparagine at position 2, e.g., a substitution at position 2 according to Kabat numbering, e.g., a Isoleucine to Asparagine, a Serine to Asparagine, or a Tyrosine to Asparagein substitution; or
(iii) a Leucine at position 4, e.g., a substitution at position 4 according to Kabat numbering, e.g., a Methionine to Leucine substitution,
wherein the substitution is relative to a human germline light chain framework region sequence.

### Claim 172 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171)

The method, or composition for use of any one of claims 98-171, wherein the anti-TCRβV antibody molecule comprises a light chain comprising a framework region, e.g., framework region 3 (FR3), comprising one, two or all (e.g., three) of:
(i) a Glycine at position 66, e.g., a substitution at position 66 according to Kabat numbering, e.g., a Lysine to Glycine, or a Serine to Glycine substitution; or
(ii) an Asparagine at position 69, e.g., a substitution at position 69 according to Kabat numbering, e.g., a Threonine to Asparagine substitution; or
(iii) a Tyrosine at position 71, e.g., a substitution at position 71 according to Kabat numbering, e.g., a Phenylalanine to Tyrosine, or Alanine to Tyrosine substitution,
wherein the substitution is relative to a human germline light chain framework region sequence.

### Claim 173 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171)

The method, or composition for use of any one of claims 98-171, wherein binding of the anti-TCRβV antibody molecule to the TCRβV region results in a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCRβV region (“a non-TCRβV-binding T cell engager”).

### Claim 174 (depends on 173)

The method, or composition for use of claim 173, wherein the non-TCRβV-binding T cell engager comprises an antibody that binds to a CD3 molecule (e.g., CD3 epsilon (CD3e) molecule); or a TCR alpha (TCRα) molecule.

### Claim 175 (depends on 173, 174)

The method, or composition for use of claim 173 or 174, wherein the cytokine profile of the first moiety comprises, one, two, three, four, five, six, seven, or all of the following:
(i) increased level, e.g., expression level, and/or activity of IL-2;
(ii) reduced level, e.g., expression level, and/or activity of IL-10;
(iii) reduced level, e.g., expression level, and/or activity of IL-6;
(iv) reduced level, e.g., expression level, and/or activity of TNFα;
(v) reduced level, e.g., expression level, and/or activity of IL-10;
(vi) a delay, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more hours delay, in increased level, e.g., expression level, and/or activity of IL-2;
(vii) a delay, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 hours delay, in increased level, e.g., expression level, and/or activity of IFNg; or
(viii) increased level, e.g., expression level, and/or activity of IL-15,
e.g., wherein (i)-(vii) are relative to the cytokine profile of the non-TCRβV-binding T cell engager.

### Claim 176 (depends on 173, 174, 175)

The method, or composition for use of any one of claims 173-175, wherein binding of the anti-TCRβV antibody molecule to the TCRβV region results in reduced cytokine storm, e.g., reduced cytokine release syndrome (CRS), as measured by an assay of Example 3, e.g., relative to the cytokine storm induced by the non-TCRβV-binding T cell engager.

### Claim 177 (depends on 173, 174, 175, 176)

The method, or composition for use of any one of claims 173-176, wherein binding of the anti-TCRβV antibody molecule to the TCRβV region results in one, two, three or all of:
(ix) reduced T cell proliferation kinetics;
(x) cell killing, e.g., target cell killing, e.g. cancer cell killing, e.g., as measured by an assay of Example 4;
(xi) increased Natural Killer (NK) cell proliferation, e.g., expansion; or
(xii) expansion, e.g., at least about 1.1-10 fold expansion (e.g., at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion), of a population of memory T cells,
e.g., relative to the non-TCRβV-binding T cell engager.

### Claim 178 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178)

The method, or composition for use of any one of claims 98-178, wherein the anti-TCRβV antibody molecule binds to an outward facing region (e.g., epitope) on a TCRβV protein, e.g., as depicted by the circled area in FIG. 24A.

### Claim 179 (depends on 178)

The method, or composition for use of claim 178, wherein the outward facing region on the TCRβV protein comprises a structurally conserved region of TCRβV, e.g., a region of TCRβV having a similar structure across one or more TCRβV subfamilies.

### Claim 180 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179)

The method, or composition for use of any one of claims 98-179, the method further comprises administering (e.g., sequentially, simultaneously or concurrently) a second agent, e.g., therapeutic agent, e.g., as described herein.

### Claim 181 (depends on 180)

The method, or composition for use of claim 180, wherein the second agent, e.g., therapeutic agent, comprises a chemotherapeutic agent, a biologic agent, hormonal therapy), radiation, or surgery.

### Claim 182 (depends on 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134)

The method, or composition for use of any one of claims 98 to 134, wherein the disease is a cancer, e.g., a solid tumor or a hematological cancer, or a metastatic lesion.

### Claim 183 (depends on 175)

The method of claim 175, wherein the cancer antigen is BCMA or FcRH5.