# US 2019/0169260 A1 · Human Leukocyte Antigen Restricted Gamma Delta T Cell Receptors and Methods of Use Thereof > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0169260 A1 - Document ID: US20190169260A1 - Status: Published application - Kind: A1 - Application number: 16/215,452 - Filed: 2018-12-10 - Published: 2019-06-06 - Earliest claimed: 2016-06-10 - Assignees: Gadeta B.V. - Applicants: Gadeta B.V. - Inventors: Jürgen Herbert Ernst Kuball; Guido Joris Jan Kierkels; Zsolt Sebestyen - Web page: https://patentgrep.com/patent/US20190169260A1 ## CPC - C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules} - A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells - A61K 40/32: T-cell receptors [TCR] - A61K 40/42: Cancer antigens - A61P 35/00: Antineoplastic agents - C07K 14/7051: {T-cell receptor (TcR)-CD3 complex} - C07K 16/30: from tumour cells - C12N 5/0634: {Cells from the blood or the immune system} - C12N 5/0636: {T lymphocytes} - C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]} - C12N 15/62: DNA sequences coding for fusion proteins - C12N 15/907: {in mammalian cells} - C12Q 1/6809: Methods for determination or identification of nucleic acids involving differential detection - G01N 33/56977: {HLA or MHC typing} - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 2239/31: characterized by the route of administration - A61K 2239/38: characterised by the dose, timing or administration schedule - A61K 2239/49: Breast - C07K 2317/32: specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor - G01N 2800/7028: Cancer - 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) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract Disclosed herein are compositions and methods of treating a subject with cancer. The compositions and methods utilize immunoresponsive cells to effect killing of tumor cells. ## Claims ### Claim 1 A composition comprising a polypeptide construct that selectively binds a human leukocyte antigen (HLA) molecule or portion thereof on a target cell when said HLA molecule is complexed to at least one additional HLA molecule on said target cell, wherein said polypeptide construct does not bind an uncomplexed HLA molecule, and wherein said polypeptide construct is expressed on a cell or synthesized. ### Claim 2 (depends on 1) The composition of claim 1, wherein said HLA molecule is an HLA-A serotype or variant thereof. ### Claim 3 (depends on 2) The composition of claim 2, wherein said HLA-A serotype is HLA-A*24. ### Claim 4 (depends on 3) The composition of claim 3, wherein said HLA-A*24 is HLA-A*24:02. ### Claim 5 (depends on 1, 2, 3, 4) The composition of any one of claims 1 to 4, wherein said complex comprises a clustering of said HLA molecule. ### Claim 6 (depends on 1, 2, 3, 4) The composition of any one of claims 1 to 4, wherein said complex comprises a K-conformation. ### Claim 7 (depends on 6) The composition of claim 6, wherein said K-conformation comprises at least one of differential special distribution or differential clustering of said HLA molecule when compared to a comparable normal cell. ### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7) The composition of any one of claims 1 to 7, wherein said polypeptide construct binds at least one co-receptor. ### Claim 9 (depends on 8) The composition of claim 8, wherein said at least one co-receptor is selected from a group consisting of: CD8, CD4, CD28, CCR, and CXCR4. ### Claim 10 (depends on 9) The composition of claim 9, wherein said at least one co-receptor is CD8. ### Claim 11 (depends on 10) The composition of claim 10, wherein said at least one co-receptor comprises a least one of CD8 alpha or CD8beta. ### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11) The composition of any one of claims 1 to 11, wherein said target cell is a cancer cell. ### Claim 13 (depends on 12) The composition of claim 12, wherein said cancer cell aberrantly expresses said HLA molecule. ### Claim 14 (depends on 13) The composition of claim 13, wherein said aberrant expression comprises said K-conformation on said target cell and said aberrant expression and said complexing is not present on a comparable normal cell. ### Claim 15 (depends on 13) The composition of claim 13, wherein said aberrant expression comprises at least one of structure, mobility, flexibility, or compartmentalization as compared to a non-aberrantly expressed HLA on a comparable normal cell. ### Claim 16 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15) The composition of any one of claims 1 to 15, wherein said complexing is detected by flow cytometry or microscopy. ### Claim 17 (depends on 12, 13, 14, 15, 16) The composition of any one of claims 12 to 16, wherein said cancer cell overexpresses said HLA as compared to said comparable normal cell. ### Claim 18 (depends on 17) The composition of claim 17, wherein said overexpression comprises from about 1% to about 100% expression on a population of said cancer cell as detected by flow cytometry. ### Claim 19 (depends on 17, 18) The composition of any one of claims 17 to 18, wherein said overexpression comprises a positive detection of said HLA molecule by immunohistochemistry (IHC) analysis. ### Claim 20 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19) The composition of any one of claims 1 to 19, wherein said polypeptide construct is expressed on immune cells. ### Claim 21 (depends on 20) The composition of claim 20, wherein said immune cells are from a myeloid or lymphoid lineage. ### Claim 22 (depends on 21) The composition of claim 21, wherein said immune cells are from a lymphoid lineage. ### Claim 23 (depends on 22) The composition of claim 22, wherein said immune cells from a lymphoid lineage are at least one of natural killer (NK) cells, B cells, or T cells. ### Claim 24 (depends on 20, 21, 22, 23) The composition of any one of claims 20 to 23, wherein said immune cells are a plurality of T cells. ### Claim 25 (depends on 24) The composition of claim 24, wherein said plurality of T cells are engineered αβ T cells. ### Claim 26 (depends on 20, 21, 22, 23, 24, 25) The composition of any one of claims 20 to 25, wherein said immune cells are virally modified to express said polypeptide construct. ### Claim 27 (depends on 20, 21, 22, 23, 24, 25, 26) The composition of any one of claims 20 to 26, wherein said immune cells are non-virally modified to express said polypeptide construct. ### Claim 28 (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) The composition of any one of claims 1 to 27, wherein said polypeptide construct encodes at least a portion of a T cell receptor (TCR), antibody, chimeric antigen receptor (CAR), B cell receptor, and any combination thereof. ### Claim 29 (depends on 28) The composition of claim 28, wherein said at least a portion of a TCR is an engineered TCR. ### Claim 30 (depends on 28, 29) The composition of any one of claims 28 to 29, wherein said TCR is a γδTCR. ### Claim 31 (depends on 30) The composition of claim 30, wherein said γδTCR is a γ9δ2TCR or γ5δ1TCR. ### Claim 32 (depends on 30, 31) The composition of any one of claims 30 to 31, wherein said γδTCR is exogenous to said immune cell. ### Claim 33 (depends on 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32) The composition of any one of claims 20 to 32, wherein said immune cells are expanded. ### Claim 34 (depends on 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33) The composition of any one of claims 20 to 33, wherein said immune cells are administered to a subject in need thereof. ### Claim 35 (depends on 34) The composition of claim 34, wherein said subject in need thereof received a lymphodepleting regime prior to said administration of said immune cells. ### Claim 36 (depends on 35) The composition of claim 35, wherein said lymphodepleting regime comprises an administration of cyclophosphamide, fludarabine, radiation, or a combination thereof. ### Claim 37 (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) The composition of any one of claims 1 to 36, wherein said polypeptide construct comprises at least one of a γ-TCR polypeptide sequence, a δ-TCR polypeptide sequence, variants and fragments thereof ### Claim 38 (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) The composition of any one of claims 1 to 37, wherein said polypeptide construct comprises a CDR3 region of a γ-TCR polypeptide sequence selected from the list in Tables 2 and 6, a CDR3 region of a δ-TCR polypeptide sequence selected from the list in Tables 2 and 5, variants, and fragments thereof. ### Claim 39 (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) The composition of any one of claims 1 to 38, wherein said polypeptide construct comprises a sequence with at least from about 80%, 90%, 95%, 98%, to about 99% sequence identity to a sequence selected from the sequences in the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, amino acids 19-309 of SEQ ID NO: 4, amino acids 21-293 of SEQ ID NO: 5 and SEQ ID NO: 6 to SEQ ID NO: 428. ### Claim 40 (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) The composition of any one of claims 1 to 39, wherein said composition is administered in combination with at least one additional therapeutic agent to said subject in need thereof. ### Claim 41 (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) The composition of any one of claims 1 to 40, wherein said composition is a pharmaceutical composition. ### Claim 42 (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) A pharmaceutical composition comprising: a. the composition of any one of claims 1 to 41; and b. at least one of: an excipient, a diluent, or a carrier. ### Claim 43 (depends on 40) The pharmaceutical composition of claim 40, wherein the pharmaceutical composition is administered in unit dosage form. ### Claim 44 (depends on 42, 43) The pharmaceutical composition of any one of claims 42 to 43, wherein said pharmaceutical composition is in the form of a tablet, a liquid, a syrup, an oral formulation, an intravenous formulation, an intranasal formulation, a subcutaneous formulation, an inhalable respiratory formulation, a suppository, and any combination thereof. ### Claim 45 (depends on 44) The pharmaceutical composition of claim 44, wherein said pharmaceutical composition is administered in the form of an infusion. ### Claim 46 (depends on 45) The pharmaceutical composition of claim 45, wherein said administering of said pharmaceutical composition at least partially ameliorates a disease or condition in said subject in need thereof. ### Claim 47 (depends on 46) The pharmaceutical composition of claim 46, wherein said amelioration comprises a reduction in tumor size by at least about 30% as measured by computerized tomography (CT) scan. ### Claim 48 (depends on 47) The pharmaceutical composition of claim 47, wherein said amelioration comprises stabilizing tumor size as measured by a less than 10% change in a baseline measurement of a diameter of a tumor lesion as measured by computerized tomography (CT) scan. ### Claim 49 A method of treating a subject in need thereof comprising administering to said subject: an effective amount of a pharmaceutical composition comprising a polypeptide construct that binds a human leukocyte antigen (HLA) molecule complexed to at least one additional HLA molecule, and wherein said polypeptide construct does not bind an uncomplexed HLA molecule. ### Claim 50 (depends on 49) The method of claim 49, wherein said HLA molecule is of an HLA-A serotype or variant thereof. ### Claim 51 (depends on 50) The method of claim 50, wherein said HLA-A is HLA-A*24. ### Claim 52 (depends on 51) The method of claim 51, wherein said HLA-A*24 is HLA-A*24:02. ### Claim 53 (depends on 49, 50, 51, 52) The method of any one of claims 49 to 52, wherein said polypeptide construct comprises at least one of a γ-TCR polypeptide sequence, a δ-TCR polypeptide sequence, variants and fragments thereof ### Claim 54 (depends on 49, 50, 51, 52, 53) The method of any one of claims 49 to 53, wherein said polypeptide construct comprises a CDR3 region of a γ-TCR polypeptide sequence selected from the list in Tables 2 and 6, a CDR3 region of a δ-TCR polypeptide sequence selected from the list in Tables 2 and 5, variants, and fragments thereof. ### Claim 55 (depends on 49, 50, 51, 52, 53, 54) The method of any one of claims 49 to 54, wherein said polypeptide construct comprises a sequence with from about 80%, 90%, 95%, 98%, to about 99% sequence identity to a sequence selected from the sequences in the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, amino acids 19-309 of SEQ ID NO: 4, amino acids 21-293 of SEQ ID NO: 5 and SEQ ID NO: 6 to SEQ ID NO: 428. ### Claim 56 (depends on 49, 50, 51, 52, 53, 54, 55) The method of any one of claims 49 to 55, further comprising administering at least one of a cytokine, chemotherapy, radiation, or a combination thereof to said subject in need thereof. ### Claim 57 (depends on 56) The method of claim 56, wherein said cytokine is interleukin-2. ### Claim 58 (depends on 56, 57) The method of any one of claims 56 to 57, wherein said chemotherapy comprises at least one of cyclophosphamide or fludarabine. ### Claim 59 (depends on 49, 50, 51, 52, 53, 54, 55, 56, 57, 58) The method of any one of claims 49 to 58, wherein said polypeptide construct is lyophilized. ### Claim 60 (depends on 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59) The method of any one of claims 49 to 59, further comprising an adjuvant, diluent, carrier, or a combination thereof. ### Claim 61 A method of treating a disease comprising aberrant HLA-A*24 expression comprising administering a first therapeutic agent that binds at least a portion of a human leukocyte antigen (HLA)-A*24, and at least one of: subsequently re-administering said first therapeutic agent, and administering a second therapeutic agent. ### Claim 62 (depends on 61) The method of claim 61, wherein said first therapeutic agent comprises at least a portion of a T cell receptor (TCR), antibody, chimeric antigen receptor (CAR), B cell receptor, and any combination thereof. ### Claim 63 (depends on 62) The method of claim 62, wherein said at least a portion of a TCR is an αβTCR or a γδTCR. ### Claim 64 (depends on 63) The method of claim 63, wherein said TCR is a γδTCR. ### Claim 65 (depends on 61, 62, 63, 64) The method of any one of claims 61 to 64, wherein said first therapeutic agent is an engineered cell expressing said γδTCR. ### Claim 66 (depends on 65) The method of claim 65, wherein said engineered cell is from a lymphoid lineage or myeloid lineage. ### Claim 67 (depends on 66) The method of claim 66, wherein said engineered cell is from a lymphoid lineage and is selected from a natural killer (NK) cell, B cell, or T cell. ### Claim 68 (depends on 67) The method of claim 67, wherein said engineered cell is a T cell. ### Claim 69 (depends on 61, 62, 63, 64, 65, 66, 67, 68) The method of any one of claims 61 to 68, wherein said first therapeutic agent binds a cancer cell when said HLA-A*24 is complexed to at least one additional HLA molecule. ### Claim 70 (depends on 61, 62, 63, 64, 65, 66, 67, 68, 69) The method of any one of claims 61 to 69, wherein said re-administration is performed from about 24 hours to about 1 year after said administering a first therapeutic agent. ### Claim 71 (depends on 61, 62, 63, 64, 65, 66, 67, 68, 69, 70) The method of any one of claims 61 to 70, further comprising detecting a level of said first therapeutic agent by at least one of quantitative PCR (qPCR) or flow cytometry. ### Claim 72 (depends on 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71) The method of any one of claims 61 to 71, wherein said second therapeutic agent is selected from the group consisting of: chemotherapeutic, radiotherapeutic, or immunotherapeutic. ### Claim 73 (depends on 72) The method of claim 72, wherein said second therapeutic agent is an immunotherapeutic. ### Claim 74 An engineered cell comprising: a genomic alteration encoding a polypeptide construct that selectively binds a human leukocyte antigen (HLA) molecule or portion thereof on a target cell when said HLA molecule is complexed to at least one additional HLA molecule on said target cell, wherein said polypeptide construct does not bind an uncomplexed HLA molecule. ### Claim 75 (depends on 74) The engineered cell of claim 74, wherein said HLA comprises class I, class II, or a combination thereof. ### Claim 76 (depends on 75) The engineered cell of claim 75, wherein said HLA comprises class I (HLA-I). ### Claim 77 (depends on 76) The engineered cell of claim 76, wherein said HLA-I comprises HLA-A. ### Claim 78 (depends on 77) The engineered cell of claim 77, wherein said HLA-A is HLA-A*24. ### Claim 79 (depends on 78) The engineered cell of claim 78, wherein said HLA-A*24 allele comprises HLA-A*24:02. ### Claim 80 (depends on 74, 75, 76, 77, 78, 79) The engineered cell of any one of claims 74 to 79, wherein said genomic alteration comprises a knock in comprising a viral introduction of said polypeptide construct. ### Claim 81 (depends on 80) The engineered cell of claim 80, wherein said viral introduction comprises a virus selected from the group consisting of a lentivirus, retrovirus, adenovirus, and any combination thereof. ### Claim 82 (depends on 81) The engineered cell of claim 81, wherein said viral introduction comprises a retrovirus. ### Claim 83 (depends on 74, 75, 76, 77, 78, 79, 80, 81, 82) The engineered cell of any one of claims 74 to 82, wherein said polypeptide construct comprises at least one γδTCR or fragment or variant thereof. ### Claim 84 (depends on 83) The engineered cell of claim 83, wherein said γδTCR comprises a γ-TCR polypeptide sequence selected from the list in Tables 2 and 6, a CDR3 region of a δ-TCR polypeptide sequence selected from the list in Tables 2 and 5, variants, and fragments thereof. ### Claim 85 (depends on 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84) The engineered cell of any one of claims 74 to 84, wherein said polypeptide construct selectively binds said HLA on said target cell, in the presence of at least one additional peptide and/or at least one co-receptor. ### Claim 86 (depends on 85) The engineered cell of claim 85, wherein said at least one co-receptor is selected from a group consisting of: CD8, CD4, CD28, CCR, and CXCR4. ### Claim 87 (depends on 86) The engineered cell of claim 86, wherein said at least one co-receptor is CD8. ### Claim 88 (depends on 87) The engineered cell of claim 87, wherein said at least one co-receptor comprises at least one of CD8 alpha or CD8 beta. ### Claim 89 (depends on 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88) A population of cells comprising the engineered cell of any one of claims 74 to 88. ### Claim 90 (depends on 89) The population of claim 89, wherein from about 60% to about 100% of said engineered cells express said polypeptide construct. ### Claim 91 (depends on 89, 90) The population of any one of claims 89 to 90, wherein said engineered cells are a plurality of αβ T cells. ### Claim 92 (depends on 89, 90, 91) The population of any one of claims 89 to 91, wherein when said population is administered to a subject in need thereof a cancer is controlled, reduced, or eliminated. ### Claim 93 (depends on 89, 90, 91, 92) The population of any one of claims 89 to 92, wherein when said population is administered to a subject in need thereof a viral infection is controlled, reduced, or eliminated. ### Claim 94 (depends on 93) The population of claim 93, wherein said administration is effective in reducing tumor size by at least 30% as measured by computerized tomography (CT) scan. ### Claim 95 (depends on 93) The population of claim 93, wherein said administration is effective in stabilizing tumor size as measured by a less than 10% change in a baseline measurement of a diameter of a tumor lesion as measured by computerized tomography (CT) scan. ### Claim 96 (depends on 92, 93, 94, 95) The population of any one of claims 92 to 95, wherein from about 5×104 to about 1×1012 cells are administered to said subject in need thereof. ### Claim 97 (depends on 92, 93, 94, 95, 96) The population of any one of claims 92 to 96, wherein said administration extends a life of said subject in need thereof from about 1 week to about 50 years as compared to an untreated subject. ### Claim 98 (depends on 89, 90, 91, 92, 93, 94, 95, 96, 97) The population of any one of claims 89 to 97, wherein said engineered cells are inhibited by a binding of an antibody. ### Claim 99 (depends on 98) The population of claim 98, wherein said binding of an antibody reduces toxicity associated with said administration of said engineered cells. ### Claim 100 A polynucleic acid comprising a sequence that is at least 90%, 95%, 97% or 99% identical to a sequence encoding a polypeptide sequence of at least one of SEQ ID NO: 2, SEQ ID NO: 3, amino acids 19-309 of SEQ ID NO: 4, or amino acids 21-293 of SEQ ID NO: 5. ### Claim 101 An engineered cell comprising a receptor sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to at least one of SEQ ID NO: 2, SEQ ID NO: 3, amino acids 19-309 of SEQ ID NO: 4, or amino acids 21-293 of SEQ ID NO: 5. ### Claim 102 An engineered cell comprising at least a portion of a receptor with a sequence that is at least 95%, 96%, 97%, 98%, or 99% identical to at least one of SEQ ID NO: 2, SEQ ID NO: 3, amino acids 19-309 of SEQ ID NO: 4, amino acids 21-293 of SEQ ID NO: 5 and SEQ ID NO: 6 to SEQ ID NO: 428. ### Claim 103 (depends on 102) The engineered cell of claim 102, wherein said engineered cell is expanded to a population of engineered cells. ### Claim 104 (depends on 103) The engineered cell of claim 103, wherein said population of engineered cells are formulated into a pharmaceutical composition. ### Claim 105 A polypeptide that selectively binds a human leukocyte antigen (HLA) molecule or portion thereof on a target cell when said HLA molecule is complexed to at least one additional HLA molecule on said target cell, wherein said polypeptide does not bind an uncomplexed HLA molecule. ### Claim 106 (depends on 105) A polypeptide according to claim 105, wherein said HLA molecule is an HLA-A serotype or variant thereof, preferably wherein said HLA-A serotype is HLA-A*24, more preferably, wherein said HLA-A*24 is HLA-A*24:02. ### Claim 107 (depends on 105, 106) A polypeptide according to claim 105 or 106, wherein said target cell is a cancer cell, preferably wherein said cancer cell aberrantly expresses said HLA molecule. ### Claim 108 (depends on 105, 106, 107) A polypeptide according to any one of claims 105 to 107, wherein the polypeptide is a δT-cell receptor chain or part thereof comprising a CDR3 region, said δT-cell receptor chain or part thereof being represented by an amino acid sequence, said amino acid sequence comprising at least 60% sequence identity or similarity with any one of amino acid sequence SEQ ID NO: 3, amino acids 21-293 of SEQ ID NO: 5, or SEQ ID NOs: 6 to 237. ### Claim 109 (depends on 105, 106, 107) A polypeptide according to any one of claims 105 to 107, wherein the polypeptide is a γT-cell receptor chain or part thereof comprising a CDR3 region, said δT-cell receptor chain or part thereof being represented by an amino acid sequence, said amino acid sequence comprising at least 60% sequence identity or similarity with any one of amino acid sequence SEQ ID NO: 2, amino acids 19-309 of SEQ ID NO: 4, or SEQ ID NOs: 238 to 428. ### Claim 110 (depends on 108, 109) A T cell receptor (TCR), preferably an engineered TCR comprising: a. a δT-cell receptor chain or part thereof as defined in claim 108 and b. a γT-cell receptor chain or part thereof as defined in claim 109. ### Claim 111 (depends on 105, 106, 107, 108, 109, 110) A nucleic acid molecule encoding the polypeptide as defined in any one of claims 105 to 109 or the TCR of claim 110. ### Claim 112 (depends on 111) A nucleic acid construct comprising the nucleic acid molecule of claim 111. ### Claim 113 (depends on 112) A cell comprising the nucleic acid construct of claim 112. ### Claim 114 (depends on 105, 106, 107, 108, 109, 110, 111, 112, 113) A polypeptide as defined in claims 105 to 109, a TCR as defined in claim 110, a nucleic acid molecule of claim 111, a nucleic acid construct of claim 112 or a cell of claim 113 for use as a medicament. ### Claim 115 (depends on 105, 106, 107, 108, 109, 110, 111, 112, 113) A polypeptide as defined in claims 105 to 109, a TCR as defined in claim 110, a nucleic acid molecule of claim 111, a nucleic acid construct of claim 112 or a cell of claim 113 for use as a medicament against cancer or an infection. ### Claim 116 (depends on 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 113) A method of reducing toxicity associated with the administration of the engineered cell of any one of claims 74 to 88, or the cell of claim 113, comprising administration of at least one antibody or portion thereof to a subject in need thereof. ### Claim 117 (depends on 116) The method of claim 116, wherein said antibody is a blocking antibody or neutralizing antibody. ### Claim 118 (depends on 116, 117) The method of any one of claims 116 to 117, wherein said antibody or portion thereof inhibits binding of said engineered cell or said cell to a cell expressing HLA-A*24:02. ### Claim 119 (depends on 118) The method of claim 118, wherein said cell expressing HLA-A*24:02 is at least one of a cancer cell or a comparable normal cell. ### Claim 120 (depends on 116, 117, 118, 119) The method of any one of claims 116 to 119, wherein said administration of at least one antibody or portion thereof reduces a level of at least one of cytokine release syndrome (CRS), B-Cell Aplasia, and Tumor Lysis Syndrome (TLS) in said subject in need thereof. ### Claim 121 (depends on 116, 117, 118, 119, 120) The method of any one of claims 116-120, wherein said at least one antibody binds said HLA-A*24:02 completely or partially. ### Claim 122 (depends on 121) The method of claim 121, wherein said antibody is a human antibody, a humanized antibody or fragment or variant thereof. ### Claim 123 (depends on 122) The method of claim 122, wherein said variant is an scFv, or scFab. ### Claim 124 (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) The composition or pharmaceutical composition of any one of claims 1-48, wherein said composition or pharmaceutical composition retains activity when stored in a sealed container at 25° C. or 4° C. for a predetermined amount of time in an atmosphere having a predetermined relative humidity. ### Claim 125 (depends on 124) The composition or pharmaceutical composition of claim 124, wherein said predetermined relative humidity is 30%, 40%, 50%, 60%, 70%, 75%, 80%, 90% or 95% relative humidity. ### Claim 126 (depends on 124, 125) The composition or pharmaceutical composition of any one of claims 124-125, wherein said predetermined time is at least 1 month, 2 months, 3 months, 6 months, 1 year, 1.5 years, 2 years, 2.5 years or 3 years. ### Claim 127 (depends on 124, 125, 126) The composition or pharmaceutical composition of any one of claims 124-126 said composition or pharmaceutical composition retains at least 50%, 60%, 70%, 80% or 90% activity as determined by binding to an HLA molecule which complexed to at least one additional HLA molecule.