# US 2021/0275584 A1 · Immune cell compositions and methods of use for treating viral and other infections

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- Number: US 2021/0275584 A1
- Document ID: US20210275584A1
- Status: Published application
- Kind: A1
- Application number: 16/329,142
- Filed: 2017-08-29
- Published: 2021-09-09
- Earliest claimed: 2016-08-30
- Assignees: Memorial Sloan Kettering Cancer Center
- Applicants: Memorial Sloan Kettering Cancer Center
- Inventors: Prasad S. Adusumilli
- Web page: https://patentgrep.com/patent/US20210275584A1

## CPC

- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/36: Immune checkpoint inhibitors
- A61K 40/4255: {Mesothelin [MSLN]}
- A61K 40/4276: {Prostate specific membrane antigen [PSMA]}
- A61P 31/12: Antivirals
- A61P 31/18: for HIV
- C07K 14/70503: {Immunoglobulin superfamily}
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 14/71: for growth factors; for growth regulators
- C07K 16/30: from tumour cells
- C12N 5/0636: {T lymphocytes}
- A61K 2239/28: Expressing multiple CARs, TCRs or antigens
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/46: characterised by the cancer treated
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/32: fusions with soluble part of a cell surface receptor, "decoy receptors"
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/70: containing domain for protein-protein interaction
- C12N 2510/00: Genetically modified cells
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Disclosed herein are cells that are immune cells, which cells recombinantly express a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, and optionally recombinantly express a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen. In certain embodiments, the immune cell is an immunostimulatory cell, such as a T cell. In certain embodiments, the immune cell is an immunoinhibitory cell, such as a regulatory T cell. Also disclosed herein are immune cells that recognize and are sensitized to a viral antigen, which immune cells recombinantly express a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell. The cells can be sensitized to an antigen that is a viral antigen. Additionally provided are methods of using such cells to treat a viral infection in a subject in need thereof.

## Claims

### Claim 1

A cell that is an immunostimulatory cell or precursor cell thereof, which cell recombinantly expresses (a) a chimeric antigen receptor (CAR), and (b) a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the CAR binds to a viral antigen.

### Claim 2

A population of immunostimulatory cells or precursor cells thereof, which cell population comprises cells that recombinantly express (a) a chimeric antigen receptor (CAR), and (b) a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the CAR binds to a viral antigen.

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

The cell or cell population of claim 1 or 2, wherein the immunostimulatory cell is a T cell.

### Claim 4 (depends on 1, 2, 3)

The cell or cell population of any one of claims 1-3, wherein the precursor cell is a hematopoietic stem or hematopoietic progenitor cell.

### Claim 5 (depends on 1, 2, 3, 4)

The cell or cell population of any one of claims 1-4, wherein the immunostimulatory cell is a cytotoxic T lymphocyte (CTL).

### Claim 6 (depends on 1, 2)

The cell or cell population of claim 1 or 2, wherein the cell is a T cell.

### Claim 7 (depends on 1, 2)

The cell or cell population of claim 1 or 2, wherein the cell is a Natural Killer (NK) cell.

### Claim 8 (depends on 1, 2)

The cell or cell population of claim 1 or 2, wherein the cell is a memory T cell.

### Claim 9 (depends on 8)

The cell or cell population of claim 8, wherein the memory T cell is a memory CD8+ T cell.

### Claim 10

A T cell that recognizes and is sensitized to a viral antigen, which T cell recombinantly expresses a dominant negative form of an inhibitor of a T cell-mediated immune response.

### Claim 11 (depends on 10)

The T cell of claim 10 which is immunostimulatory.

### Claim 12 (depends on 10, 11)

The T cell of claim 10 or 11 which is CD4+.

### Claim 13 (depends on 10, 11)

The T cell of claim 10 or 11 which is CD8+.

### Claim 14

A population of T cells, which cell population comprises T cells that recognize and are sensitized to a viral antigen and which recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response.

### Claim 15 (depends on 14)

The population of claim 14, wherein the T cells are immunostimulatory.

### Claim 16 (depends on 14, 15)

The population of claim 14 or 15, wherein the T cells are CD4+.

### Claim 17 (depends on 14, 15)

The population of claim 14 or 15, wherein the T cells are CD8+.

### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)

The cell or cell population of any one of claims 1-17, which is derived from a human.

### Claim 19 (depends on 18)

The cell or cell population of claim 18, wherein the viral antigen is of a virus that is a human pathogen.

### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)

The cell or cell population of any one of claims 1-19, wherein the viral antigen can elicit an immune response in a human subject infected with the virus.

### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)

The cell or cell population of any one of claims 1-20, wherein the viral antigen is selected from the group consisting of a human immunodeficiency virus (HIV) antigen, a hepatitis B virus (HBV) antigen, a hepatitis C virus (HCV) antigen, a herpes simplex virus (HSV) antigen, a varicella zoster virus (VZV) antigen, an adenovirus antigen, a cytomegalovirus (CMV) antigen, and an Epstein-Barr virus (EBV) antigen.

### Claim 22 (depends on 21)

The cell or cell population of claim 21, wherein the viral antigen is a HIV antigen selected from the group consisting of group-specific antigen (gag) protein, p55, p24, p18, envelope glycoprotein (env), gp160, gp120, gp41, reverse transcriptase (pol), p66, and p31.

### Claim 23 (depends on 21)

The cell or cell population of claim 21, wherein the viral antigen is a HBV antigen selected from the group consisting of HBV envelope protein S, HBV envelope protein M, HBV envelope protein L, and the S domain of HBV envelope protein S, M or L.

### Claim 24 (depends on 21)

The cell or cell population of claim 21, wherein the viral antigen is a HCV antigen selected from the group consisting of core protein, envelope protein E1, envelope protein E2, NS2, NS3, NS4, and NS5.

### Claim 25 (depends on 21)

The cell or cell population of claim 21, wherein the viral antigen is a HSV antigen selected from the group consisting of gE, gI, gB, gD, gH, gL, gC, gG, gK, gM, and the extracellular domain of gE.

### Claim 26 (depends on 21)

The cell or cell population of claim 21, wherein the viral antigen is a VZV antigen selected from the group consisting of gE and gI.

### Claim 27 (depends on 21)

The cell or cell population of claim 21, wherein the viral antigen is an adenovirus antigen selected from the group consisting of hexon protein and penton protein.

### Claim 28 (depends on 21)

The cell or cell population of claim 21, wherein the viral antigen is a CMV antigen selected from the group consisting of pp65, immediate early (IE) antigen, and IE1.

### Claim 29 (depends on 21)

The cell or cell population of claim 21, wherein the viral antigen is an EBV antigen selected from the group consisting of latent membrane protein 2 (LMP2), Epstein-Barr nuclear antigen 1 (EBNA1), and BZLF1.

### Claim 30 (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)

The cell or cell population of any one of claims 1-29, wherein the inhibitor of a cell-mediated immune response is an immune checkpoint inhibitor.

### Claim 31 (depends on 30)

The cell or cell population of claim 30, wherein the immune checkpoint inhibitor is selected from the group consisting of programmed death 1 (PD-1), cytotoxic T lymphocyte antigen-4 (CTLA-4), B- and T-lymphocyte attenuator (BTLA), T cell immunoglobulin mucin-3 (TIM-3), lymphocyte-activation protein 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), natural killer cell receptor 2B4 (2B4), and CD160.

### Claim 32 (depends on 31)

The cell or cell population of claim 31, wherein the immune checkpoint inhibitor is PD-1.

### Claim 33 (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)

The cell or cell population of any one of claims 1-29, wherein the inhibitor of a cell-mediated immune response is transforming growth factor β (TGF-β) receptor.

### Claim 34 (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)

The cell or cell population of any one of claims 1-33, wherein the cell further recombinantly expresses a suicide gene.

### Claim 35 (depends on 34)

The cell or cell population of claim 34, wherein the suicide gene comprises inducible Caspase 9.

### Claim 36

A regulatory T cell that recognizes and is sensitized to a viral antigen, which regulatory T cell recombinantly expresses a dominant negative form of an inhibitor of a regulatory T cell-mediated immune response.

### Claim 37

A population of regulatory T cells, which cell population comprises T cells that recognize and are sensitized to a viral antigen and which recombinantly express a dominant negative form of an inhibitor of a regulatory T cell-mediated immune response.

### Claim 38 (depends on 36, 37)

The cell or cell population of claim 36 or 37, wherein the regulatory T cell is isolated from a subject having a chronic viral infection.

### Claim 39

A regulatory T cell isolated from a subject having a viral infection, which regulatory T cell recombinantly expresses a dominant negative form of an inhibitor of a regulatory T cell-mediated immune response.

### Claim 40

A population of regulatory T cells isolated from a subject having a viral infection, which cell population comprises regulatory T cells which recombinantly express a dominant negative form of an inhibitor of a regulatory T cell-mediated immune response.

### Claim 41 (depends on 39, 40)

The cell or cell population of claim 39 or 40, which is derived from a human.

### Claim 42 (depends on 41)

The cell or cell population of claim 41, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 43 (depends on 39, 40, 41, 42)

The cell or cell population of any one of claims 39-42, wherein the viral infection is a chronic viral infection.

### Claim 44 (depends on 39, 40, 41, 42, 43)

The cell or cell population of any one of claims 39-43, wherein the viral infection is infection with HCV, HBV, HIV, HSV, VZV, adenovirus, CMV or EBV.

### Claim 45

An immunoinhibitory cell, which cell is isolated from a subject having a viral infection, which immunoinhibitory cell recombinantly expresses a dominant negative form of an inhibitor of an immunoinhibitory cell-mediated immune response.

### Claim 46

A population of immunoinhibitory cells isolated from a subject having a viral infection, which cell population comprises immunoinhibitory cells which recombinantly express a dominant negative form of an inhibitor of an immunoinhibitory cell-mediated immune response.

### Claim 47 (depends on 45, 46)

The cell or cell population of claim 45 or 46, which is derived from a human.

### Claim 48 (depends on 47)

The cell or cell population of claim 47, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 49 (depends on 45, 46, 47, 48)

The cell or cell population of any one of claims 45-48, wherein the viral infection is a chronic viral infection.

### Claim 50 (depends on 45, 46)

The cell or cell population of claim 45 or 46, wherein the immunoinhibitory cell is a regulatory T cell.

### Claim 51 (depends on 45, 46, 47, 48, 49)

The cell or cell population of any one of claims 45-49, wherein the immunoinhibitory cell recognizes and is sensitized to a viral antigen of the virus of the viral infection.

### Claim 52 (depends on 45, 46, 47, 48, 49, 50)

The cell or cell population of any one of claims 45-50, wherein the immunoinhibitory cell recombinantly expresses a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen of the virus of the viral infection.

### Claim 53 (depends on 36, 37, 38, 39, 40, 41, 42, 43, 44, 50, 51, 52)

The cell or cell population of any one of claims 36-44 or 50-52, wherein the regulatory T cell is a human CD4+CD25+ T cell.

### Claim 54 (depends on 36, 37, 38, 39, 40, 41, 42, 43, 44, 50, 51, 52)

The cell or cell population of any one of claims 36-44 or 50-52, wherein the regulatory T cell is a human CD4+CD127lo/−CD25+ T cell.

### Claim 55

A polyclonal population of human regulatory T cells that are CD4+CD25+, are sensitized to a viral antigen, and recombinantly express a dominant negative form of an inhibitor of a regulatory T cell-mediated immune response.

### Claim 56 (depends on 55)

The polyclonal population of cells of claim 55, wherein the human regulatory T cells are CD127lo/−.

### Claim 57 (depends on 36, 37, 38)

The cell or cell population of any one of claims 36-38, which is derived from a human.

### Claim 58 (depends on 57)

The cell or cell population of claim 57, wherein the viral antigen is of a virus that is a human pathogen.

### Claim 59 (depends on 36, 37, 38, 51, 52, 53, 54, 55, 56, 57, 58)

The cell or cell population of any one of claims 36-38 or 51-58, wherein the viral antigen can elicit an immune response in a human subject infected with the virus.

### Claim 60 (depends on 36, 37, 38, 51, 52, 53, 54, 55, 56, 57, 58, 59)

The cell or cell population of any one of claims 36-38 or 51-59, wherein the viral antigen is selected from the group consisting of a hepatitis C virus (HCV) antigen, a human immunodeficiency virus (HIV) antigen, a hepatitis B virus (HBV) antigen, a herpes simplex virus (HSV) antigen, a varicella zoster virus (VZV) antigen, an adenovirus antigen, a cytomegalovirus (CMV) antigen, and an Epstein-Barr virus (EBV) antigen.

### Claim 61 (depends on 60)

The cell or cell population of claim 60, wherein the viral antigen is a HCV antigen selected from the group consisting of core protein, envelope protein E1, envelope protein E2, NS2, NS3, NS4, and NS5.

### Claim 62 (depends on 60)

The cell or cell population of claim 60, wherein the viral antigen is a HIV antigen selected from the group consisting of group-specific antigen (gag) protein, p55, p24, p18, envelope glycoprotein (env), gp160, gp120, gp41, reverse transcriptase (pol), p66, and p31.

### Claim 63 (depends on 60)

The cell or cell population of claim 60, wherein the viral antigen is a HBV antigen selected from the group consisting of HBV envelope protein S, HBV envelope protein M, HBV envelope protein L, and the S domain of HBV envelope protein S, M or L.

### Claim 64 (depends on 60)

The cell or cell population of claim 60, wherein the viral antigen is a HSV antigen selected from the group consisting of gE, gI, gB, gD, gH, gL, gC, gG, gK, gM, and the extracellular domain of gE.

### Claim 65 (depends on 60)

The cell or cell population of claim 60, wherein the viral antigen is a VZV antigen selected from the group consisting of gE and gI.

### Claim 66 (depends on 60)

The cell or cell population of claim 60, wherein the viral antigen is an adenovirus antigen selected from the group consisting of hexon protein and penton protein.

### Claim 67 (depends on 60)

The cell or cell population of claim 60, wherein the viral antigen is a CMV antigen selected from the group consisting of pp65, immediate early (IE) antigen, and IE1.

### Claim 68 (depends on 60)

The cell or cell population of claim 60, wherein the viral antigen is an EBV antigen selected from the group consisting of latent membrane protein 2 (LMP2), Epstein-Barr nuclear antigen 1 (EBNA1), and BZLF1.

### Claim 69 (depends on 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68)

The cell or cell population of any one of claims 36-68, wherein the inhibitor of a cell-mediated immune response is an immune checkpoint inhibitor.

### Claim 70 (depends on 69)

The cell or cell population of claim 69, wherein the immune checkpoint inhibitor is selected from the group consisting of programmed death 1 (PD-1), cytotoxic T lymphocyte antigen-4 (CTLA-4), B- and T-lymphocyte attenuator (BTLA), T cell immunoglobulin mucin-3 (TIM-3), lymphocyte-activation protein 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), natural killer cell receptor 2B4 (2B4), and CD160.

### Claim 71 (depends on 70)

The cell or cell population of claim 70, wherein the immune checkpoint inhibitor is PD-1.

### Claim 72 (depends on 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68)

The cell or cell population of any one of claims 36-68, wherein the inhibitor of a cell-mediated immune response is transforming growth factor β (TGF-β) receptor.

### Claim 73 (depends on 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72)

The cell or cell population of any one of claims 36-72, wherein the cell further recombinantly expresses a suicide gene.

### Claim 74 (depends on 73)

The cell or cell population of claim 73, wherein the suicide gene comprises inducible Caspase 9.

### Claim 75

A cell that is an immunostimulatory cell or precursor cell thereof, which cell recombinantly expresses:
(a) a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen;
(b) a first dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the first dominant negative form lacks an intracellular signaling domain and is a polypeptide comprising (i) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, and (ii) a transmembrane domain; and
(c) a second dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the second dominant negative form is a polypeptide comprising (i) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, (ii) a transmembrane domain, and (iii) a co-stimulatory signaling domain, wherein the co-stimulatory signaling domain is carboxy-terminal to the transmembrane domain of the dominant negative form.

### Claim 76

A population of immunostimulatory cells or precursor cells thereof, which cell population comprises cells that recombinantly express:
(a) a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen;
(b) a first dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the first dominant negative form lacks an intracellular signaling domain and is a polypeptide comprising (i) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, and (ii) a transmembrane domain; and
(c) a second dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the second dominant negative form is a polypeptide comprising (i) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, (ii) a transmembrane domain, and (iii) a co-stimulatory signaling domain, wherein the co-stimulatory signaling domain is carboxy-terminal to the transmembrane domain of the dominant negative form.

### Claim 77 (depends on 75, 76)

The cell or population of claim 75 or 76, wherein the co-stimulatory signaling domain of the second dominant negative form is the intracellular signaling domain of 4-1BB.

### Claim 78 (depends on 75, 76, 77)

The cell or population of any one of claims 75-77, wherein the CAR comprises a co-stimulatory signaling domain.

### Claim 79 (depends on 78)

The cell or population of claim 78, wherein the co-stimulatory signaling domain of the second dominant negative form is different from the co-stimulatory signaling domain of the CAR.

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

The cell or population of claim 78 or 79, wherein the co-stimulatory signaling domain of the CAR is the intracellular signaling domain of CD28.

### Claim 81 (depends on 75, 76, 77, 78, 79, 80)

The cell or cell population of any one of claims 75-80, wherein the immunostimulatory cell is a T cell.

### Claim 82 (depends on 75, 76, 77, 78, 79, 80, 81)

The cell or cell population of any one of claims 75-81, wherein the precursor cell is a hematopoietic stem or hematopoietic progenitor cell.

### Claim 83 (depends on 75, 76, 77, 78, 79, 80, 81, 82)

The cell or cell population of any one of claims 75-82, wherein the immunostimulatory cell is a cytotoxic T lymphocyte (CTL).

### Claim 84 (depends on 75, 76, 77, 78, 79, 80)

The cell or cell population of any one of claims 75-80, wherein the cell is a Natural Killer (NK) cell.

### Claim 85 (depends on 75, 76, 77, 78, 79, 80)

The cell or cell population of any one of claims 75-80, wherein the cell is a memory T cell.

### Claim 86 (depends on 85)

The cell or cell population of claim 85, wherein the memory T cell is a memory CD8+ T cell.

### Claim 87

An immunoinhibitory cell, which cell is isolated from a subject having a viral infection, which immunoinhibitory cell recombinantly expresses:
(a) a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen of the virus of the viral infection;
(b) a first dominant negative form of an inhibitor of a cell-mediated immune response of the immunoinhibitory cell, wherein the first dominant negative form lacks an intracellular signaling domain and is a polypeptide comprising (i) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, and (ii) a transmembrane domain; and
(c) a second dominant negative form of an inhibitor of a cell-mediated immune response of the immunoinhibitory cell, wherein the second dominant negative form is a polypeptide comprising (i) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, (ii) a transmembrane domain, and (iii) a co-stimulatory signaling domain, wherein the co-stimulatory signaling domain is carboxy-terminal to the transmembrane domain of the dominant negative form.

### Claim 88

A population of immunoinhibitory cells isolated from a subject having a viral infection, which cell population comprises immunoinhibitory cells which recombinantly express:
(a) a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen of the virus of the viral infection;
(b) a first dominant negative form of an inhibitor of a cell-mediated immune response of the immunoinhibitory cell, wherein the first dominant negative form lacks an intracellular signaling domain and is a polypeptide comprising (i) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, and (ii) a transmembrane domain; and
(c) a second dominant negative form of an inhibitor of a cell-mediated immune response of the immunoinhibitory cell, wherein the second dominant negative form is a polypeptide comprising (i) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, (ii) a transmembrane domain, and (iii) a co-stimulatory signaling domain, wherein the co-stimulatory signaling domain is carboxy-terminal to the transmembrane domain of the dominant negative form.

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

The cell or population of claim 87 or 88, wherein the co-stimulatory signaling domain is the intracellular signaling domain of 4-1BB.

### Claim 90 (depends on 87, 88, 89)

The cell or population of any one of claims 87-89, wherein the CAR comprises a co-stimulatory signaling domain.

### Claim 91 (depends on 90)

The cell or population of claim 90, wherein the co-stimulatory signaling domain of the second dominant negative form is different from the co-stimulatory signaling domain of the CAR.

### Claim 92 (depends on 90, 91)

The cell or population of claim 90 or 91, wherein the co-stimulatory signaling domain of the CAR is the intracellular signaling domain of CD28.

### Claim 93 (depends on 87, 88, 89, 90, 91, 92)

The cell or cell population of any one of claims 87-92, which is derived from a human.

### Claim 94 (depends on 93)

The cell or cell population of claim 93, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 95 (depends on 87, 88, 89, 90, 91, 92, 93, 94)

The cell or cell population of any one of claims 87-94, wherein the viral infection is a chronic viral infection.

### Claim 96 (depends on 87, 88, 89, 90, 91, 92, 93, 94, 95)

The cell or cell population of any one of claims 87-95, wherein the immunoinhibitory cell is a regulatory T cell.

### Claim 97 (depends on 96)

The cell or cell population of claim 96, wherein the regulatory T cell is a human CD4+CD25+ T cell.

### Claim 98 (depends on 96)

The cell or cell population of claim 96, wherein the regulatory T cell is a human CD4+CD127lo/−CD25+ T cell.

### Claim 99

A cell that is an immunostimulatory cell or precursor cell thereof, which cell recombinantly expresses (a) a chimeric antigen receptor (CAR), and (b) a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the CAR binds to an antigen of a pathogen.

### Claim 100

A population of immunostimulatory cells or precursor cells thereof, which cell population comprises cells that recombinantly express (a) a chimeric antigen receptor (CAR), and (b) a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the CAR binds to an antigen of a pathogen.

### Claim 101 (depends on 99, 100)

The cell or cell population of claim 99 or 100, wherein the immunostimulatory cell is a T cell.

### Claim 102 (depends on 101)

The cell or cell population of claim 101, wherein the T cell is CD4+.

### Claim 103 (depends on 10, 11)

The cell or cell population of claim 10 or 11, wherein the T cell is CD8+.

### Claim 104 (depends on 99, 100)

The cell or cell population of claim 99 or 100, wherein the precursor cell is a hematopoietic stem or hematopoietic progenitor cell.

### Claim 105 (depends on 99, 100)

The cell or cell population of claim 99 or 100, wherein the immunostimulatory cell is a cytotoxic T lymphocyte (CTL).

### Claim 106 (depends on 99, 100)

The cell or cell population of claim 99 or 100, wherein the cell is a Natural Killer (NK) cell.

### Claim 107 (depends on 99, 100)

The cell or cell population of claim 99 or 100, wherein the cell is a memory T cell.

### Claim 108 (depends on 107)

The cell or cell population of claim 107, wherein the memory T cell is a memory CD8+ T cell.

### Claim 109

A T cell that recognizes and is sensitized to an antigen of a pathogen, which T cell recombinantly expresses a dominant negative form of an inhibitor of a T cell-mediated immune response.

### Claim 110 (depends on 109)

The T cell of claim 109 which is immunostimulatory.

### Claim 111 (depends on 109, 110)

The T cell of claim 109 or 110 which is CD4+.

### Claim 112 (depends on 109, 110)

The T cell of claim 109 or 110 which is CD8+.

### Claim 113

A population of T cells, which cell population comprises T cells that recognize and are sensitized to an antigen of a pathogen and which recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response.

### Claim 114 (depends on 113)

The population of claim 113, wherein the T cells are immunostimulatory.

### Claim 115 (depends on 113, 114)

The population of claim 113 or 114, wherein the T cells are CD4+.

### Claim 116 (depends on 113, 114)

The population of claim 113 or 114, wherein the T cells are CD8+.

### Claim 117 (depends on 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116)

The cell or cell population of any one of claims 99-116, which is derived from a human.

### Claim 118 (depends on 117)

The cell or cell population of claim 117, wherein the pathogen is a human pathogen.

### Claim 119 (depends on 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118)

The cell or cell population of any one of claims 99-118, wherein the antigen of the pathogen can elicit an immune response in a human subject infected with the pathogen.

### Claim 120 (depends on 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119)

The cell or cell population of any one of claims 99-119, wherein the pathogen is selected from the group consisting of a bacterium, fungus, and protozoan.

### Claim 121 (depends on 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120)

The cell or cell population of any one of claims 99-120, wherein the inhibitor of a cell-mediated immune response is an immune checkpoint inhibitor.

### Claim 122 (depends on 121)

The cell or cell population of claim 121, wherein the immune checkpoint inhibitor is selected from the group consisting of programmed death 1 (PD-1), cytotoxic T lymphocyte antigen-4 (CTLA-4), B- and T-lymphocyte attenuator (BTLA), T cell immunoglobulin mucin-3 (TIM-3), lymphocyte-activation protein 3 (LAG-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), natural killer cell receptor 2B4 (2B4), and CD160.

### Claim 123 (depends on 122)

The cell or cell population of claim 122, wherein the immune checkpoint inhibitor is PD-1.

### Claim 124 (depends on 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120)

The cell or cell population of any one of claims 99-120, wherein the inhibitor of a cell-mediated immune response is transforming growth factor β (TGF-β) receptor.

### Claim 125 (depends on 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)

The cell or cell population of any one of claims 99-124, wherein the cell further recombinantly expresses a suicide gene.

### Claim 126 (depends on 125)

The cell or cell population of claim 125, wherein the suicide gene comprises inducible Caspase 9.

### Claim 127 (depends on 1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A pharmaceutical composition comprising a therapeutically effective amount of the cell of any one of claims 1, 3-13 or 15-35; and a pharmaceutically acceptable carrier.

### Claim 128 (depends on 2, 3, 4, 5, 6, 7, 8, 9, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35)

A pharmaceutical composition comprising a therapeutically effective amount of the population of cells of any one of claims 2-9 or 14-35; and a pharmaceutically acceptable carrier.

### Claim 129 (depends on 36, 38, 39, 41, 42, 43, 44, 50, 53, 54, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74)

A pharmaceutical composition comprising a therapeutically effective amount of the regulatory T cell of any one of claims 36, 38, 39, 41-44, 50, 53, 54 or 57-74; and a pharmaceutically acceptable carrier.

### Claim 130 (depends on 37, 38, 40, 41, 42, 43, 44, 50, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74)

A pharmaceutical composition comprising a therapeutically effective amount of the population of regulatory T cells of any one of claims 37, 38, 40-44, 50 or 53-74; and a pharmaceutically acceptable carrier.

### Claim 131 (depends on 45, 47, 48, 49, 51, 52)

A pharmaceutical composition comprising a therapeutically effective amount of the immunoinhibitory cell of any one of claims 45, 47-49, 51 or 52; and a pharmaceutically acceptable carrier.

### Claim 132 (depends on 46, 47, 48, 49, 51, 52)

A pharmaceutical composition comprising a therapeutically effective amount of the population of immunoinhibitory cells of any one of claims 46-49, 51 or 52; and a pharmaceutically acceptable carrier.

### Claim 133 (depends on 75, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86)

A pharmaceutical composition comprising a therapeutically effective amount of the immunostimulatory cell of any one of claims 75 or 77-86; and a pharmaceutically acceptable carrier.

### Claim 134 (depends on 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86)

A pharmaceutical composition comprising a therapeutically effective amount of the population of immunostimulatory cells of any one of claims 76-86; and a pharmaceutically acceptable carrier.

### Claim 135 (depends on 87, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98)

A pharmaceutical composition comprising a therapeutically effective amount of the immunoinhibitory cell of any one of claims 87 or 89-98; and a pharmaceutically acceptable carrier.

### Claim 136 (depends on 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98)

A pharmaceutical composition comprising a therapeutically effective amount of the population of immunoinhibitory cells of any one of claims 88-98; and a pharmaceutically acceptable carrier.

### Claim 137 (depends on 99, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126)

A pharmaceutical composition comprising a therapeutically effective amount of the cell of any one of claims 99, 101-112 or 117-126; and a pharmaceutically acceptable carrier.

### Claim 138 (depends on 100, 101, 102, 103, 104, 105, 106, 107, 108, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126)

A pharmaceutical composition comprising a therapeutically effective amount of the population of cells of any one of claims 100-108 or 113-126; and a pharmaceutically acceptable carrier.

### Claim 139 (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)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the cell or cell population of any one of claims 1-35, wherein the viral antigen is an antigen associated with the viral infection.

### Claim 140 (depends on 127, 128)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 127 or 128, wherein the viral antigen is an antigen associated with the viral infection.

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

The method of claim 139 or 140, wherein the subject is a human.

### Claim 142 (depends on 141)

The method of claim 141, wherein the viral infection is infection with a virus that is a human pathogen.

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

The method of any one of claims 139-142, wherein the viral infection is infection with HIV, HBV, HCV, HSV, VZV, adenovirus, CMV or EBV.

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

The method of any one of claims 139-143, wherein expression of the dominant negative form promotes production of virus-specific memory cells.

### Claim 145 (depends on 36, 37, 38, 39, 40, 41, 42, 43, 44, 50, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the regulatory T cell or population of regulatory T cells of any one of claims 36-44, 50 or 53-74, wherein the viral antigen is an antigen associated with the viral infection.

### Claim 146 (depends on 129, 130)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 129 or 130, wherein the viral antigen is an antigen associated with the viral infection.

### Claim 147 (depends on 45, 46, 47, 48, 49, 51, 52)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the immunoinhibitory cell or population of immunoinhibitory cells of any one of claims 45-49, 51 or 52.

### Claim 148 (depends on 131, 132)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 131 or 132.

### Claim 149 (depends on 145, 146, 147, 148)

The method of any one of claims 145-148, wherein the subject is a human.

### Claim 150 (depends on 149)

The method of claim 149, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 151 (depends on 145, 146, 147, 148, 149, 150)

The method of any one of claims 145-150, wherein the viral infection is a chronic viral infection.

### Claim 152 (depends on 145, 146, 147, 148, 149, 150, 151)

The method of any one of claims 145-151, wherein the viral infection is infection with HCV, HIV, HBV, HSV, VZV, adenovirus, CMV or EBV.

### Claim 153

A method of treating a viral infection in a subject in need thereof, comprising:
(a) isolating virus-specific T cells from the subject;
(b) expressing in the cells a dominant negative form of PD-1; and
(c) administering the cells to the subject.

### Claim 154

A method of treating a viral infection in a subject in need thereof, comprising:
(a) isolating virus-specific T cells from the subject;
(b) expressing in the cells a dominant negative form of PD-1, wherein expression of the dominant negative form of PD-1 promotes production of virus-specific memory cells; and
(c) administering the cells to the subject.

### Claim 155

A method of treating a viral infection in a subject in need thereof, comprising:
(a) isolating regulatory T cells from a subject having a chronic viral infection;
(b) expressing in the cells a dominant negative form of PD-1; and
(c) administering the cells to the subject.

### Claim 156 (depends on 153, 154, 155)

The method of any one of claims 153-155, wherein the subject is a human.

### Claim 157 (depends on 156)

The method of claim 156, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 158 (depends on 153, 154, 155, 156, 157)

The method of any one of claims 153-157, wherein the viral infection is infection with HIV, HBV, HCV, HSV, VZV, adenovirus, CMV or EBV.

### Claim 159 (depends on 153, 156, 157)

The method of any one of claims 153, 156 or 157, wherein the viral infection is infection with HIV.

### Claim 160 (depends on 154, 156, 157)

The method of any one of claims 154, 156 or 157, wherein the viral infection is infection with HBV.

### Claim 161 (depends on 155, 156, 157)

The method of any one of claims 155-157, wherein the viral infection is infection with HCV.

### Claim 162 (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)

The method of any one of claims 139-161, wherein the administering is by intrapleural administration, intravenous administration, subcutaneous administration, intranodal administration, intrahepatic administration, intrathecal administration, intraperitoneal administration, intracranial administration, or direct administration to the thymus.

### 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 one of claims 139-162, wherein the cell is administered in a dose in the range of 104 to 1010 cells per kilogram of body weight.

### Claim 164 (depends on 163)

The method of claim 163, wherein the dose is in the range of 3×105 to 3×106 cells per kilogram of body weight.

### Claim 165 (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, 163, 164)

The method of any one of claims 139-164, wherein the cell or cell population is autologous to the subject.

### Claim 166 (depends on 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the cell or cell population of any one of claims 75-86, wherein the viral antigen is an antigen associated with the viral infection.

### Claim 167 (depends on 133, 134)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 133 or 134, wherein the viral antigen is an antigen associated with the viral infection.

### Claim 168 (depends on 166, 167)

The method of claim 166 or 167, wherein the subject is a human.

### Claim 169 (depends on 168)

The method of claim 168, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 170 (depends on 166, 167, 168, 169)

The method of any one of claims 166-169, wherein the viral infection is infection with HIV, HBV, HCV, HSV, VZV, adenovirus, CMV or EBV.

### Claim 171 (depends on 166, 167, 168, 169, 170)

The method of any one of claims 166-170, wherein expression of the first dominant negative form promotes production in the subject of virus-specific memory cells.

### Claim 172 (depends on 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the cell or cell population of any one of claims 87-98, wherein the viral antigen is an antigen associated with the viral infection.

### Claim 173 (depends on 135, 136)

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 135 or 136, wherein the viral antigen is an antigen associated with the viral infection.

### Claim 174 (depends on 172, 173)

The method of claim 172 or 173, wherein the subject is a human.

### Claim 175 (depends on 174)

The method of claim 174, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 176 (depends on 172, 173, 174, 175)

The method of any one of claims 172-175, wherein the viral infection is infection with HIV, HBV, HCV, HSV, VZV, adenovirus, CMV or EBV.

### Claim 177 (depends on 172, 173, 174, 175, 176)

The method of any one of claims 172-176, wherein expression of the first dominant negative form promotes production in the subject of virus-specific memory cells.

### Claim 178

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of:
(a) a first cell or first population of said first cell, wherein the first cell is an immunostimulatory cell and recombinantly expresses (i) a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen and wherein the viral antigen is an antigen associated with the viral infection, and (ii) a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the dominant negative form lacks an intracellular signaling domain and is a polypeptide comprising (A) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, and (B) a transmembrane domain; and
(b) a second cell or second population of said second cell, wherein the second cell is an immunostimulatory cell and recombinantly expresses (i) a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen and wherein the viral antigen is an antigen associated with the viral infection, and (ii) a dominant negative form of an inhibitor of a cell-mediated immune response of the immunostimulatory cell, wherein the dominant negative form is a polypeptide comprising (A) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, (B) a transmembrane domain, and (C) a co-stimulatory signaling domain, wherein the co-stimulatory signaling domain is carboxy-terminal to the transmembrane domain of the dominant negative form.

### Claim 179 (depends on 178)

The method of claim 178, wherein the subject is a human.

### Claim 180 (depends on 179)

The method of claim 179, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 181 (depends on 178, 179, 180)

The method of any one of claims 178-180, wherein the viral infection is infection with HIV, HBV, HCV, HSV, VZV, adenovirus, CMV or EBV.

### Claim 182

A method of treating a viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of:
(a) a first cell or first population of said first cell, wherein the first cell is an immunoinhibitory cell and recombinantly expresses (i) a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen and wherein the viral antigen is an antigen associated with the viral infection, and (ii) a dominant negative form of an inhibitor of a cell-mediated immune response of the immunoinhibitory cell, wherein the dominant negative form lacks an intracellular signaling domain and is a polypeptide comprising (A) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, and (B) a transmembrane domain; and
(b) a second cell or second population of said second cell, wherein the second cell is an immunoinhibitory cell and recombinantly expresses (i) a chimeric antigen receptor (CAR), wherein the CAR binds to a viral antigen and wherein the viral antigen is an antigen associated with the viral infection, and (ii) a dominant negative form of an inhibitor of a cell-mediated immune response of the immunoinhibitory cell, wherein the dominant negative form is a polypeptide comprising (A) at least a portion of an extracellular domain of an immune checkpoint inhibitor, wherein the portion comprises the ligand binding region, (B) a transmembrane domain, and (C) a fusion to a co-stimulatory signaling domain, wherein the co-stimulatory signaling domain is carboxy-terminal to the transmembrane domain of the dominant negative form.

### Claim 183 (depends on 182)

The method of claim 182, wherein the subject is a human.

### Claim 184 (depends on 183)

The method of claim 183, wherein the viral infection is infection with a virus that is a human pathogen.

### Claim 185 (depends on 182, 183, 184)

The method of any one of claims 182-184, wherein the viral infection is infection with HIV, HBV, HCV, HSV, VZV, adenovirus, CMV or EBV.

### Claim 186 (depends on 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185)

The method of any one of claims 166-185, wherein the cell or cell population is autologous to the subject.

### Claim 187 (depends on 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)

A method of treating an infection caused by a pathogen in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the cell or cell population of any one of claims 99-126, wherein the antigen of the pathogen to which the CAR binds or to which the T cell is sensitized is an antigen of the pathogen causing the infection.

### Claim 188 (depends on 137, 138)

A method of treating an infection caused by a pathogen in a subject in need thereof, comprising administering to the subject the pharmaceutical composition of claim 137 or 138, wherein the antigen of the pathogen to which the CAR binds or to which the T cell is sensitized is an antigen of the pathogen causing the infection.

### Claim 189 (depends on 187, 188)

The method of claim 187 or 188, wherein the subject is a human.

### Claim 190 (depends on 189)

The method of claim 189, wherein the pathogen causing the infection is a human pathogen.