JPWO2021097325A5 - - Google Patents

Description

[0697] Sequence alignment of eight functional human TCRVβ6 family sequences shows three unique amino acids in subfamily 6-5 (Figure 107), with positions Q79, L101, and S102 unique to TCRVβ6-5. It is. Alanine substitutions at positions Q79, L101, and S102 significantly decreased binding of antibody H131 to the TCR compared to the WT receptor (Figures 108A-108D).
This specification includes the disclosure of the following inventions.
[Item 1] A method of reducing or altering an immune response induced by adoptive T cell therapy in a subject, the method comprising:
(a) administering adoptive T cell therapy to the subject, wherein the adoptive T cell therapy comprises a plurality of αβ T cell receptors (TCRs) expressing αβ T cell receptors (TCR) comprising a T cell receptor beta variable chain (TCRβV) region; comprising a T cell of
(b) administering to the subject a first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region and activates the T cell;
including methods.
[Item 2] The first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region reduces or reduces the immune response induced by the adoptive T cell therapy in the subject. The method of item 1, wherein the method is administered in an amount sufficient to cause the change.
[Item 3] The decrease is in a cytokine or chemokine in a sample from the subject after administration of the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region. prior to administration of the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region to the subject; 3. The method of item 1 or 2, wherein the level of the cytokine or chemokine is compared to the level of the cytokine or chemokine in a sample from the subject after administration of T cell therapy.
[Item 4] A method of mitigating an excessive immune response induced by adoptive T cell therapy in a subject, the method comprising:
(a) administering adoptive T cell therapy to the subject, wherein the adoptive T cell therapy comprises a plurality of αβ T cell receptors (TCRs) expressing αβ T cell receptors (TCR) comprising a T cell receptor beta variable chain (TCRβV) region; comprising a T cell of
(b) administering to the subject a first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region and activates the T cell;
including methods.
[Item 5] The first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region suppresses the excessive immune response induced by the adoptive T cell therapy in the subject. The method of item 4, wherein the method is administered in an amount sufficient to provide relief.
[Item 6] The relaxation of a cytokine or chemokine in a sample from the subject after administration of the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region. prior to administration of said first agent comprising a domain that specifically binds to a T cell receptor beta variable chain (TCRβV) region to said subject and said adoptive T cell in comparison to the level of said cytokine or chemokine in a control sample from said subject prior to administration of therapy, wherein said cytokine or chemokine level comprises said domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region. said level of cytokine or chemokine from a sample from said subject after administration of one of the agents is 1000 times, 500 times, 400 times, 300 times, 200 times, 100 times, 50 times the level in said control sample. , 25 times, 10 times, 5 times, or within 2 times, the method according to item 4 or 5.
[Item 7] A method of treating cancer in a subject, comprising:
(a) administering adoptive T cell therapy to the subject, wherein the adoptive T cell therapy comprises a plurality of αβ T cell receptors (TCRs) expressing αβ T cell receptors (TCR) comprising a T cell receptor beta variable chain (TCRβV) region; comprising a T cell of
(b) administering to the subject a first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region and activates the T cell;
including methods.
[Item 8] The first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region reduces or reduces the immune response induced by the adoptive T cell therapy in the subject. The method of item 7, wherein the method is administered in an amount sufficient to cause the change.
[Item 9] The decrease is determined by measuring the level of a cytokine or chemokine in a sample from the subject after administration of the first agent, and the decrease is determined in the absence of the first agent. 9. The method of item 8, wherein the level of the cytokine or chemokine is in comparison to a control sample from a subject who received the adoptive T cell therapy.
[Item 10] The first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region has a sufficient amount to ameliorate the symptoms induced by the adoptive T cell therapy. 8. The method of item 7, wherein the method is administered to the subject in an amount.
[Item 11] The improvement in symptoms is determined by measuring the level of a cytokine or chemokine in a sample from the subject after administration of the first agent, and the decrease is determined by measuring the level of a cytokine or chemokine in a sample from the subject after administration of the first agent. 11. The method of item 10, wherein the level of the cytokine or chemokine in the sample from the subject before administration of the agent and after administration of the adoptive T cell therapy.
[Item 12] A method for treating cancer in a subject in need of cancer treatment, comprising:
(a) administering to the subject a first pharmaceutical composition comprising adoptive T cell therapy that induces an immune response against cancer cells in the subject, wherein the adoptive T cell therapy comprising a plurality of T cells expressing an αβ T cell receptor (TCR) comprising a variable chain (TCRβV) region;
(b) administering to the subject a second pharmaceutical composition comprising a first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region and activates the T cell; step and
including methods.
[Item 13] The second pharmaceutical composition comprising the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region is capable of administering the adoptive T cell therapy in the subject. 13. The method of item 12, wherein the method is administered to the subject in an amount sufficient to reduce the immune response induced by.
[Item 14] The decrease is determined by measuring the level of a cytokine or chemokine in a sample from the subject after administration of the second pharmaceutical composition, and the decrease is determined by measuring the level of a cytokine or chemokine in a sample from the subject after administration of the second pharmaceutical composition. 14. The method of item 13, in comparison to the level of said cytokine or chemokine in a control sample from a subject who was administered said first pharmaceutical composition in the absence of.
[Item 15] The second pharmaceutical composition comprising the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region is induced by the adoptive T cell therapy. 13. The method according to item 12, wherein the method is administered to the subject in an amount sufficient to ameliorate the symptoms of the condition.
[Item 16] The decrease is determined by measuring the level of a cytokine or chemokine in a sample from the subject after administration of the second pharmaceutical composition, and the decrease is determined by measuring the level of cytokine or chemokine in a sample from the subject after administration of the second pharmaceutical composition to the subject. 16. The method of item 15, wherein the level of the cytokine or chemokine in a sample from the subject before administration of the first pharmaceutical composition and after administration of the first pharmaceutical composition.
[Item 17] The first pharmaceutical composition contains 0.1 to 10.0×10 ⁶ cells per 1 kg of body weight of the subject, and 0.1 to 9.0×10 ⁶ cells per 1 kg of body weight of the subject. cells, 0.1 to 8.0×10 ⁶ cells per kg of body weight of the subject, 0.1 to 7.0×10 6 ^cells per kg of body weight of the subject, 0 cells per kg of body weight of the subject. .1 to 6.0×10 ⁶ cells, 0.1 to 5.0×10 6 ^cells per kg of said subject's body weight, 0.1 to 4.0×10 ⁶ cells per kg of said subject's body weight. cells, 0.1 to 3.0 x 10 cells per kg of body weight of the subject ^, 0.1 to 2.0 x 10 cells per kg of body weight of the subject , or 0.1 to 2.0 x 10 cells per kg of body weight of the subject ^. The method according to any of items 12 to 16, comprising 0.1 to 1.0×10 ⁶ cells.
[Item 18] The method according to item 17, wherein the first pharmaceutical composition contains 0.2 to 5.0×10 ⁶ cells per kg of body weight of the subject.
[Item 19] The method according to item 18, wherein the first pharmaceutical composition contains 2.0 x 10 6 ^cells per kg of body weight of the subject.
[Item 20] The first pharmaceutical composition contains 0.1 to 10×10 ⁸ cells, 0.1 to 9×10 ⁸ cells, 0.1 to 8×10 ⁸ cells, 0 .1-7×10 ⁸ cells, 0.1-6×10 ⁸ cells, 0.1-5×10 ⁸ cells, 0.1-4×10 ⁸ cells, 0.1 18. The method of item 17, comprising ˜3×10 ⁸ cells, 0.1-2×10 ⁸ cells, or 0.1-1×10 ⁸ cells.
[Item 21] The method according to item 17, wherein the first pharmaceutical composition contains 0.1 to 2.5×10 ⁸ cells.
[Item 22] The method according to item 17, wherein the first pharmaceutical composition contains 0.6 to 6.0×10 ⁸ cells.
[Item 23] The method according to item 17, wherein the first pharmaceutical composition contains 2×10 ⁶ cells/kg body weight.
[Item 24] The method according to item 17, wherein the first pharmaceutical composition contains 2×10 ⁸ cells.
[Item 25] A method of reducing an immune response induced by adoptive T cell therapy in a subject, the method comprising:
(a) administering adoptive T cell therapy to the subject, wherein the adoptive T cell therapy comprises a plurality of αβ T cell receptors (TCRs) expressing αβ T cell receptors (TCR) comprising a T cell receptor beta variable chain (TCRβV) region; comprising a T cell of
(b) specifically binds to said T cell receptor beta variable chain (TCRβV) region and induces said T cell when the level of a cytokine or chemokine in a sample from said subject is at least 1000 times higher than a baseline level; administering to said subject a first agent comprising an activating domain;
including methods.
[Item 26] The first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region is sufficient to reduce the immune response induced by the adoptive T cell therapy. 26. The method of item 25, wherein the method is administered in an amount.
[Item 27] The level of the cytokine or chemokine in the sample from the subject is at least 2000-fold, 3000-fold, 4000-fold, 5000-fold, 6000-fold, 7000-fold, 8000-fold, 9000-fold, 100000-fold higher than the baseline level. 27. The method of item 25 or 26, wherein the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region is administered to the subject.
[Item 28] A method of reducing an immune response in a subject receiving adoptive T cell therapy, the method comprising:
(a) administering adoptive T cell therapy to the subject, wherein the adoptive T cell therapy comprises a plurality of αβ T cell receptors (TCRs) expressing αβ T cell receptors (TCR) comprising a T cell receptor beta variable chain (TCRβV) region; comprising a T cell of
(b) administering a first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region and activates the T cell to induce an excessive immune response induced by the adoptive cell therapy; administering to said subject an amount sufficient to reduce said first agent, said first agent comprising said domain that specifically binds said T cell receptor beta variable chain (TCRβV) region; determined by measuring the presence or severity of at least one symptom associated with the excessive immune response in the subject following administration of the T cell receptor beta variable chain (TCRβV) to the subject. ) in comparison to the presence or severity of said at least one symptom in said subject before administration of said first agent comprising said domain that specifically binds to a region and after administration of said adoptive cell therapy. A method, including steps.
[Item 29] The first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region suppresses the excessive immune response induced by the adoptive T cell therapy in the subject. 29. The method of item 28, wherein the method is administered to the subject in an amount sufficient to cause the decrease.
[Item 30] A method for alleviating an excessive immune response in a subject receiving an immunotherapeutic agent, the method comprising:
(a) administering adoptive T cell therapy to the subject, wherein the adoptive T cell therapy comprises a plurality of αβ T cell receptors (TCRs) expressing αβ T cell receptors (TCR) comprising a T cell receptor beta variable chain (TCRβV) region; comprising a T cell of
(b) administering a first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region and activates the T cell to induce an excessive immune response induced by the adoptive cell therapy; administering to said subject an amount sufficient to reduce
at least one condition wherein said alleviation is associated with said excessive immune response in said subject after administration of said first agent comprising said domain that specifically binds said T cell receptor beta variable chain (TCRβV) region. the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region; and in comparison to the severity of the at least one symptom associated with the excessive immune response in the subject prior to administration of the adoptive T cell therapy;
The at least one condition associated with the excessive immune response in the subject following administration of the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region comprises: Comparison with the at least one symptom before administration of the first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region and before administration of the adoptive T cell therapy to the subject. The less severe the method.
[Item 31] The first agent comprising the domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region suppresses the excessive immune response induced by adoptive T cell therapy in the subject. 31. The method of item 30, wherein the method is administered to the subject in an amount sufficient to provide relief.
[Item 32] The method according to any one of items 28 to 31, wherein the at least one symptom is associated with cytokine release syndrome, macrophage activation syndrome, neurotoxicity, or tumor lysis syndrome.
[Item 33] The method of item 32, wherein the at least one symptom is associated with cytokine release syndrome.
[Item 34] The at least one symptom is hemophagocytic lymphohistiocytosis (HLH), fever, nausea, vomiting, chills, hypotension, tachycardia, arrhythmia, cardiomyopathy, acute heart failure, asthenia, headache, rash. , dyspnea, encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, hallucinations, cerebral edema, hepatomegaly, hypofibroticemia, liver failure, diarrhea, 34. The method of item 33, comprising edema, stiffness, arthralgia, myalgia, acute renal failure, splenomegaly, respiratory failure, pulmonary edema, hypoxia, capillary leak syndrome, macrophage activation syndrome, or tachypnea.
[Item 35] The method of item 32, wherein the at least one symptom is associated with neurotoxicity.
[Item 36] The method of item 35, wherein the at least one symptom includes encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, or cerebral edema.
[Item 37] The method of item 32, wherein the at least one symptom is associated with macrophage activation syndrome.
[Item 38] The at least one symptom is fever, headache, lymph node enlargement, hepatosplenomegaly, coagulopathy, rash, tachycardia, arrhythmia, cardiomyopathy, lethargy, pancytopenia, liver dysfunction, disseminated vascular disease. 38. The method of item 37, comprising intracoagulation, hypofibrinogenemia, hyperferritinemia, or hypertriglyceridemia.
[Item 39] The method of item 32, wherein the at least one symptom is associated with tumor lysis syndrome.
[Item 40] The at least one symptom is nausea, vomiting, diarrhea, muscle spasm, muscle spasms, weakness, numbness, tingling, fatigue, lethargy, decreased urinary output, encephalopathy, aphasia, tremor, ataxia, The method of item 39, comprising hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, cerebral edema, or hallucinations.
[Item 41] A method for treating or alleviating a syndrome induced by adoptive T cell therapy in a subject, the method comprising:
(a) administering adoptive T cell therapy to the subject, wherein the adoptive T cell therapy comprises a plurality of αβ T cell receptors (TCRs) expressing αβ T cell receptors (TCR) comprising a T cell receptor beta variable chain (TCRβV) region; comprising a T cell of
(b) administering a first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region and activates the T cell in association with the syndrome induced by the adoptive T cell therapy; administering to said subject an amount sufficient to prevent, treat, or reduce the severity of at least one symptom of
including methods.
[Item 42] The method according to item 41, wherein the syndrome is cytokine release syndrome, macrophage activation syndrome, neurotoxicity, or tumor lysis syndrome.
[Item 43] The method according to item 42, wherein the syndrome is cytokine release syndrome.
[Item 44] The at least one symptom is hemophagocytic lymphohistiocytosis, fever, nausea, vomiting, chills, hypotension, tachycardia, arrhythmia, cardiomyopathy, acute heart failure, asthenia, headache, rash, dyspnea , encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, cerebral edema, hepatomegaly, hypofibroticemia, liver failure, diarrhea, edema, stiffness, joints Item 43, including pain, myalgia, acute renal failure, splenomegaly, respiratory failure, pulmonary edema, hypoxia, capillary leak syndrome, macrophage activation syndrome, hemophagocytic lymphohistiocytosis (HLH), or tachypnea The method described in.
[Item 45] The method according to item 41, wherein the syndrome is neurotoxicity.
[Item 46] The method of item 45, wherein the at least one symptom includes encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, or cerebral edema.
[Item 47] The method according to item 41, wherein the syndrome is macrophage activation syndrome.
[Item 48] The at least one symptom is fever, headache, lymph node enlargement, hepatosplenomegaly, coagulopathy, rash, tachycardia, arrhythmia, cardiomyopathy, lethargy, pancytopenia, liver dysfunction, disseminated vascular disease. 48. The method of item 47, comprising intracoagulation, hypofibrinogenemia, hyperferritinemia, or hypertriglyceridemia.
[Item 49] The method according to item 41, wherein the syndrome is tumor lysis syndrome.
[Item 50] The at least one symptom is nausea, vomiting, diarrhea, muscle spasms, muscle spasm, weakness, numbness, tingling, fatigue, lethargy, decreased urinary output, encephalopathy, aphasia, tremor, ataxia, 50. The method of item 49, comprising hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, cerebral edema, or hallucinations.
[Item 51] The administration of the first agent comprising a domain that specifically binds to a T cell receptor beta variable chain (TCRβV) region binds αβ T cells comprising a T cell receptor beta variable chain (TCRβV) region 51. The method of any of items 1-50, which results in an increase in the proliferation rate of said plurality of T cells expressing a receptor (TCR).
[Item 52] The T cell receptor beta variable chain, wherein the proliferation rate is administered in the absence of the first agent comprising a domain that specifically binds to a T cell receptor beta variable chain (TCRβV) region. at least 2-fold, 3-fold, 4-fold, 5-fold, 6-fold, 7-fold compared to the proliferation rate of comparable T cells expressing an αβ T-cell receptor (TCR) comprising a (TCRβV) region; The method according to item 51, wherein the increase is 8 times, 9 times, 10 times, 20 times, 50 times, 100 times.
[Item 53] A method of expanding in vivo a population of adoptively transferred T cells administered to a subject, the method comprising:
(c) administering to the subject a population of T cells capable of inducing an immune response against cancer cells in the subject;
(d) administering to the subject a first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region, the first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region; administration of said first agent comprising a domain that specifically binds is administered in the absence of said first agent comprising a domain that specifically binds to a T cell receptor beta variable chain (TCRβV) region; increasing the proliferation rate of said T cell population as compared to an equivalent T cell population;
including methods.
[Item 54] The proliferation rate of the equivalent T cell population is administered in the absence of the first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region. of item 53, which increases by at least 2 times, 3 times, 4 times, 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 20 times, 50 times, 100 times as compared to the speed. Method.
[Item 55] The method of any one of items 1-54, wherein the subject is not administered a conditioning regimen comprising at least one lymphodepleting agent.
[Item 56] The at least one lymphocyte depleting agent is cyclophosphamide, fludarabine, mechlorethamine, chlorambucil, melphalan, ifosfamide, thiotepa, hexamethylmelamine, busulfan, nitrosourea, platinum, methotrexate, azathioprine, mercaptopurine, Procarbazine, dacarbazine, temozolomide, carmustine, lomustine, streptozocin, fluorouracil, dactinomycin, anthracycline, mitomycin C, bleomycin, mitramycin, mycophenolate mofetil, rapamycin, cyclosporine, deoxyspergualine, soluble complement receptor 1 , Cobra toxin factor, compstatin, methylprednisolone, leflunomide anti-thymocyte globulin antibody, anti-CD154 antibody, anti-CD40 antibody, anti-CD20 antibody, anti-IL-6R antibody, anti-IL-6 antibody, anti-IL-2R antibody, anti-CXCR3 antibody, anti-ICOS antibody, anti-OX40 antibody, or anti-CD122 antibody, anti-C5 antibody, abatacept, belatacept, sirolimus, everolimus, tacrolimus, daclizumab, basiliximab, infliximab, eculizumab, rituximab, alemtuzumab, tocilizumab, sarilumab, or orokizumab; The method described in item 55.
[Item 57] The method according to Item 56, wherein the at least one lymphocyte depleting agent is cyclophosphamide or fludarabine.
[Item 58] The method of any of items 55 to 57, wherein the pretreatment regimen comprises at least two lymphocyte depleting agents.
[Item 59] The method according to Item 58, wherein the at least two lymphocyte depleting agents are cyclophosphamide and fludarabine.
[Item 60] The first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region is administered to the subject before, simultaneously with, or after the adoptive T cell therapy is administered to the subject. 60. The method of any of items 1-59, wherein the method is subsequently administered to the subject.
[Item 61] The first agent includes a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region, and the TCRβV region is a domain that specifically binds to the TCRβ V6 subfamily, the TCRβ V10 subfamily, or the TCRβ V12 subfamily. family, TCRβ V5 subfamily, TCRβ V7 subfamily, TCRβ V11 subfamily, TCRβ V14 subfamily, TCRβ V16 subfamily, TCRβ V18 subfamily, TCRβ V9 subfamily, TCRβ V13 subfamily, TCRβ V4 subfamily, TCRβ V3 subfamily family, TCRβ V2 subfamily, TCRβ V15 subfamily, TCRβ V30 subfamily, TCRβ V19 subfamily, TCRβ V27 subfamily, TCRβ V28 subfamily, TCRβ V24 subfamily, TCRβ V20 subfamily, TCRβ V25 subfamily, or TCRβ V29 The second drug belongs to the TCRβ V6 subfamily, the TCRβ V10 subfamily, the TCRβ V12 subfamily, the TCRβ V5 subfamily, the TCRβ V7 subfamily, the TCRβ V11 subfamily, the TCRβ V14 subfamily, and the TCRβ V16 subfamily. family, TCRβ V18 subfamily, TCRβ V9 subfamily, TCRβ V13 subfamily, TCRβ V4 subfamily, TCRβ V3 subfamily, TCRβ V2 subfamily, TCRβ V15 subfamily, TCRβ V30 subfamily, TCRβ V19 subfamily, TCRβ V27 subfamily The first 61. The method of any of items 1-60, wherein the agent and the second agent each specifically bind to TCRβV belonging to different subfamilies or different members of the same TCRβV subfamily.
[Item 62] The plurality of T cells express an αβ T cell receptor (TCR) comprising a T cell receptor beta variable chain (TCRβV) region, and the TCRβV region is a member of the TCRβ V6 subfamily, the TCRβ V10 subfamily. , TCRβ V12 subfamily, TCRβ V5 subfamily, TCRβ V7 subfamily, TCRβ V11 subfamily, TCRβ V14 subfamily, TCRβ V16 subfamily, TCRβ V18 subfamily, TCRβ V9 subfamily, TCRβ V13 subfamily, TCRβ V4 subfamily , TCRβ V3 subfamily, TCRβ V2 subfamily, TCRβ V15 subfamily, TCRβ V30 subfamily, TCRβ V19 subfamily, TCRβ V27 subfamily, TCRβ V28 subfamily, TCRβ V24 subfamily, TCRβ V20 subfamily, TCRβ V25 subfamily , or belongs to the TCRβ V29 subfamily, and the second drug belongs to the TCRβ V6 subfamily, TCRβ V10 subfamily, TCRβ V12 subfamily, TCRβ V5 subfamily, TCRβ V7 subfamily, TCRβ V11 subfamily, TCRβ V14 subfamily , TCRβ V16 subfamily, TCRβ V18 subfamily, TCRβ V9 subfamily, TCRβ V13 subfamily, TCRβ V4 subfamily, TCRβ V3 subfamily, TCRβ V2 subfamily, TCRβ V15 subfamily, TCRβ V30 subfamily, TCRβ V19 subfamily , a domain that specifically binds to a second TCRβV region of TCRβV belonging to the TCRβ V27 subfamily, TCRβ V28 subfamily, TCRβ V24 subfamily, TCRβ V20 subfamily, TCRβ V25 subfamily, or TCRβ V29 subfamily, 62. The method of any of items 1-61, wherein the first agent and the second agent each specifically bind to TCRβV belonging to different subfamilies or different members of the same TCRβV subfamily.
[Item 63] The method according to any one of items 1 to 62, wherein the subject has cancer.
[Item 64] The method according to item 63, wherein the cancer is a hematological malignant tumor.
[Item 65] The method according to Item 63, wherein the cancer is a solid tumor.
[Item 66] The cancer is bladder cancer, epithelial cancer, bone cancer, brain cancer, breast cancer, esophageal cancer, gastrointestinal cancer, leukemia, liver cancer, lung cancer, lymphoma, myeloma, or ovarian cancer. Prostate cancer, sarcoma, stomach cancer, thyroid cancer, acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, anal canal cancer, rectal cancer, eye cancer, neck cancer, and gallbladder cancer. Pleural cancer, oral cancer, vulvar cancer, colon cancer, cervical cancer, fibrosarcoma, gastrointestinal carcinoid tumor, Hodgkin lymphoma, kidney cancer, mesothelioma, mast cell tumor, melanoma, multiple According to item 63, which is sexual myeloma, nasopharyngeal cancer, non-Hodgkin's lymphoma, pancreatic cancer, peritoneal cancer, renal cancer, skin cancer, small intestine cancer, stomach cancer, testicular cancer, and thyroid cancer. Method.
[Item 67] The cancer is bladder cancer, epithelial cancer, bone cancer, brain cancer, breast cancer, esophageal cancer, gastrointestinal cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, or stomach cancer. , thyroid cancer, alveolar rhabdomyosarcoma, anal canal, rectal cancer, eye cancer, cervical cancer, gallbladder cancer, pleural cancer, oral cavity cancer, vulvar cancer, colon cancer, cervix cancer, fibrosarcoma, kidney cancer, mesothelioma, mastocytoma, melanoma, nasopharyngeal cancer, pancreatic cancer, peritoneal cancer, kidney cancer, skin cancer, small intestine cancer, or testicular cancer The method described in item 63.
[Item 68] The method according to item 63, wherein the cancer is leukemia, myeloma, or lymphoma.
[Item 69] The method according to item 68, wherein the cancer is acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or multiple myeloma.
[Item 70] The method according to any one of items 1 to 69, wherein the adoptive T cell therapy agent comprises an exogenous receptor.
[Item 71] The method according to item 70, wherein the extrinsic cell receptor is a chimeric antigen receptor (CAR) or an extrinsic T cell receptor (TCR).
[Item 72] The method according to item 71, wherein the chimeric antigen receptor (CAR) or chimeric T cell receptor (TCR) comprises an antigen binding region that specifically binds to a tumor-associated antigen.
[Item 73] The chimeric antigen receptor (CAR) or extrinsic T cell receptor (TCR) is CD19, CD123, CD22, CD30, CD171, CS-1, C-type lectin-like molecule-1, CD33, CISH, Epidermal growth factor receptor variant III (EGFRvIII), ganglioside G2 (GD2), ganglioside GD3, TNF receptor family member B cell maturation (BCMA), Tn antigen ((Tn Ag) or (GalNAcα-Ser/Thr)), prostate specific membrane antigen (PSMA), receptor tyrosine kinase-like orphan receptor 1 (ROR1), Fms-like tyrosine kinase 3 (FLT3), tumor-associated glycoprotein 72 (TAG72), CD38, CD44v6, carcinoembryonic antigen (CEA) ), epithelial cell adhesion molecule (EPCAM), B7H3 (CD276), KIT (CD117), interleukin-13 receptor subunit alpha-2, mesothelin, interleukin-11 receptor alpha (IL-11Ra), prostate stem cell antigen ( PSCA), protease serine 21, vascular endothelial growth factor receptor 2 (VEGFR2), Lewis (Y) antigen, CD24, platelet-derived growth factor receptor beta (PDGFR-beta), stage-specific embryonic antigen-4 (SSEA-4) ), CD20, folate receptor alpha, receptor tyrosine-protein kinase ERBB2 (Her2/neu), mucin 1, cell surface associated (MUC1), epidermal growth factor receptor (EGFR), neural cell adhesion molecule (NCAM), prostase , prostatic acid phosphatase (PAP), elongation factor 2 variant (ELF2M), ephrinB2, fibroblast activation protein alpha (FAP), insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAIX), proteasome (prosome, macropain) subunit, beta type, 9 (LMP2), glycoprotein 100 (gp100), breakpoint cluster region (BCR) and Abelson murine leukemia virus oncogene homolog 1 (Abl). oncogene fusion protein (bcr-abl), tyrosinase, ephrin type A receptor 2 (EphA2), fucosyl GM1, sialyl Lewis adhesion molecule (sLe), ganglioside GM3, transglutaminase 5 (TGS5), high molecular weight melanoma-associated antigen ( HMWMAA), o-acetyl-GD2 ganglioside (OAcGD2), folate receptor beta, tumor endothelial marker 1 (TEM1/CD248), tumor endothelial marker 7 related (TEM7R), claudin 6 (CLDN6), thyroid-stimulating hormone receptor ( TSHR), G protein-coupled receptor class C group 5, member D (GPRC5D), chromosome X open reading frame 61 (CXORF61), CD97, CD179a, anaplastic lymphoma kinase (ALK), polysialic acid, placenta-specific 1 (PLAC1) ), hexasaccharide moiety of GloboH glycoceramide (GloboH), mammary gland differentiation antigen (NY-BR-1), uroplakin 2 (UPK2), hepatitis A virus cellular receptor 1 (HAVCR1), adrenergic receptor beta 3 ( ADRB3), pannexin 3 (PANX3), G protein-coupled receptor 20 (GPR20), lymphocyte antigen 6 complex, locus K9 (LY6K), olfactory receptor 51E2 (OR51E2), TCR gamma alternative reading frame protein (TARP) , Wilms tumor protein (WT1), cancer/testis antigen 1 (NY-ESO-1), cancer/testis antigen 2 (LAGE-1a), melanoma-associated antigen 1 (MAGE-A1), ETS translocation located on chromosome 12p. locus variant gene 6 (ETV6-AML), sperm protein 17 (SPA17), X antigen family, member 1A (XAGE1), angiopoietin-binding cell surface receptor 2 (Tie2), melanoma cancer testis antigen-1 (MAD- CT-1), melanoma cancer testis antigen 2 (MAD-CT-2), Fos-related antigen 1, tumor protein p53 (p53), p53 variant, prostein, survivin, telomerase, prostate cancer tumor antigen-1, T Melanoma antigen 1 recognized by cells, rat sarcoma (Ras) mutant, human telomerase reverse transcriptase (hTERT), sarcoma translocation breakpoint, melanoma inhibitor of apoptosis (ML-IAP), ERG (transmembrane protease) , serine 2 (TMPRSS2) ETS fusion gene), N-acetylglucosaminyltransferase V (NA17), paired box protein Pax-3 (PAX3), androgen receptor, cyclin B1, v-myc avian myelocytomatosis virus Oncogene neuroblastoma-derived homolog (MYCN), Ras homolog family member C (RhoC), tyrosinase-related protein 2 (TRP-2), cytochrome P450 1B1 (CYP1B1), CCCTC-binding factor (zinc finger protein)-like, T cells Recognizing squamous cell carcinoma antigen 3 (SART3), pairing box protein Pax-5 (PAX5), proacrosin binding protein sp32 (OY-TES1), lymphocyte-specific protein tyrosine kinase (LCK), A kinase anchor protein 4 (AKAP) -4), synovial sarcoma, X breakpoint 2 (SSX2), receptor for advanced glycation end products (RAGE-1), renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), legumain, human papillomavirus E6 (HPV E6) , human papillomavirus E7 (HPV E7), intestinal carboxylesterase, heat shock protein 70-2 mutant (mut hsp70-2), CD79a, CD79b, CD72, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), IgA receptor. Fc fragment (FCAR or CD89), leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), CD300 molecule-like family member f (CD300LF), C-type lectin domain family 12 member A (CLEC12A), bone marrow stromal cell antigen 2 (BST2), EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2), lymphocyte antigen 75 (LY75), glypican 3 (GPC3), Fc receptor-like 5 (FCRL5), or immunoglobulin lambda-like polypeptide 73. The method according to item 72, comprising an antigen binding region that specifically binds to IGLL1 (IGLL1) antigen.
[Item 74] The method of any one of items 1-73, wherein the adoptive T cell therapy (ACT) comprises a plurality of cells that are allogeneic or autologous to the subject.
[Item 75] The method according to any one of items 1 to 74, wherein the subject has or is at risk of developing cytokine release syndrome.
[Item 76] The cytokine or chemokine is IL-6, IFNγ, TNFα, IFNα, IL-1β, IL-8, IL-10, IL-2, IL-4, IL-5, IL-7, IL- 10, IL-13, IL-15, IL-1RA, sIL1RI, sIL1RII, sIL2Rα, sgp130, sIL6R, MCP1, MIP1α, MIP1β, MIG, GCSF, IP10, sTNFRI, sTNFRII, HGF, VEGF, sCD30, or GM -CSF The method according to any one of items 3, 6, 9, 11, 14, 16, or 27, wherein
[Item 77] The first agent comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region is an antibody, a functional fragment thereof, or a functional variant thereof. Any method described.
[Item 78] The antibody is a full-length antibody, Fab, (Fab)2, (Fab')2, Fv, (Fv)2, scFv, diabody, triabody, minibody, scFv-Fc fusion, cross Mab , a tandem diabody (TandAb), a duobody, a strand exchange engineered domain body (SEEDbody), a dual affinity retargeting molecule (DART), or a dual variable domain immunoglobulin or (DVD). the method of.
[Item 79] The method according to item 77 or 78, wherein the antibody binds to at least one Fc receptor.
[Item 80] The method of item 71, wherein the antibody exhibits at least one effector function.
[Item 81] The method according to item 77 or 78, wherein the antibody is a variant that does not bind to at least one Fc receptor that the corresponding wild-type antibody binds to.
[Item 82] The method of item 81, wherein the antibody lacks at least one effector function.
[Item 83] The method according to any one of items 1 to 82, wherein the sample is a blood sample or a serum sample.
[Item 84] A method of reducing cytokine or chemokine release in a subject in need of reduction of cytokine or chemokine release induced by adoptive T cell therapy, comprising:
(a) measuring a first level of a cytokine or chemokine in a first sample from the subject prior to administering the adoptive T cell therapy to the subject;
(b) administering said adoptive T cell therapy to said subject, said adoptive T cell therapy expressing an αβ T cell receptor (TCR) comprising a T cell receptor beta variable chain (TCRβV) region; comprising a plurality of T cells;
(c) measuring a second level of the cytokine or chemokine in a second sample from the subject after administering the adoptive T cell therapy to the subject;
(d) comparing said first level and said second level to determine whether said subject has or is suffering from at least one condition associated with an exaggerated immune response induced by said adoptive T cell therapy; a step of determining the risk of developing the disease;
(e) an agonist comprising a domain that specifically binds to the T cell receptor beta variable chain (TCRβV) region if said subject is determined to have or be at risk of developing said at least one condition; administering to the subject a first agent comprising: wherein the agonist ameliorates the at least one symptom;
including methods.
[Item 85] The method of item 84, wherein the at least one condition is associated with cytokine release syndrome, macrophage activation syndrome, neurotoxicity, or tumor lysis syndrome.
[Item 86] The at least one symptom is hemophagocytic lymphohistiocytosis, fever, nausea, vomiting, chills, hypotension, tachycardia, arrhythmia, cardiomyopathy, acute heart failure, asthenia, headache, rash, dyspnea , encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, cerebral edema, hepatomegaly, hypofibroticemia, liver failure, diarrhea, edema, stiffness, joints Item 84, including pain, myalgia, acute renal failure, splenomegaly, respiratory failure, pulmonary edema, hypoxia, capillary leak syndrome, macrophage activation syndrome, hemophagocytic lymphohistiocytosis (HLH), or tachypnea or the method described in 85.
[Item 87] The plurality of T cells expressing an αβ T cell receptor (TCR) comprising a T cell receptor beta variable chain (TCRβV) region of the adoptive cell therapy of items 1-86, wherein the method of claim 1 is expanded ex vivo by contacting with an agent comprising a first domain that specifically binds to the TCR beta variable chain (TCRβV) region, thereby generating a first population of T cells. Any method described.
[Item 88] The first drug belongs to the TCRβ V6 subfamily, TCRβ V10 subfamily, TCRβ V12 subfamily, TCRβ V5 subfamily, TCRβ V7 subfamily, TCRβ V11 subfamily, TCRβ V14 subfamily, TCRβ V16 subfamily , TCRβ V18 subfamily, TCRβ V9 subfamily, TCRβ V13 subfamily, TCRβ V4 subfamily, TCRβ V3 subfamily, TCRβ V2 subfamily, TCRβ V15 subfamily, TCRβ V30 subfamily, TCRβ V19 subfamily, TCRβ V27 subfamily , a domain that specifically binds to the TCRβV region of a first TCRβV belonging to the TCRβ V28 subfamily, the TCRβ V24 subfamily, the TCRβ V20 subfamily, the TCRβ V25 subfamily, or the TCRβ V29 subfamily, and the second agent TCRβ V6 subfamily, TCRβ V10 subfamily, TCRβ V12 subfamily, TCRβ V5 subfamily, TCRβ V7 subfamily, TCRβ V11 subfamily, TCRβ V14 subfamily, TCRβ V16 subfamily, TCRβ V18 subfamily, TCRβ V9 subfamily family, TCRβ V13 subfamily, TCRβ V4 subfamily, TCRβ V3 subfamily, TCRβ V2 subfamily, TCRβ V15 subfamily, TCRβ V30 subfamily, TCRβ V19 subfamily, TCRβ V27 subfamily, TCRβ V28 subfamily, TCRβ V24 subfamily the first agent and the second agent each include a domain that specifically binds to a second TCRβV region of TCRβV belonging to the TCRβV family, TCRβ V20 subfamily, TCRβ V25 subfamily, or TCRβ V29 subfamily; 88. The method of item 87, wherein the method specifically binds to TCRβV belonging to different subfamilies or different members of the same TCRβV subfamily.
[Item 89] The method according to item 87 or 88, wherein the contacting includes incubating or culturing the plurality of T cells with the first agent.
[Item 90] The contacting comprises contacting the plurality of T cells with the first agent for at least about 10 minutes, 20 minutes, 30 minutes, 1 hour, 6 hours, 10 hours, 12 hours, 24 hours, 36 hours. 90. The method of item 89, comprising incubating or culturing for 48 hours, 72 hours, 5 days, 7 days, 10 days, 14 days, 15 days, or 30 days.
[Item 91] The contact may cause the plurality of T cells to be exposed to the first drug for up to about 10 minutes, 20 minutes, 30 minutes, 1 hour, 6 hours, 10 hours, 12 hours, 24 hours, 36 hours. Item 87 or 88, comprising incubating or culturing for 48 hours, 72 hours, 5 days, 7 days, 10 days, 12 days, 14 days, 15 days, 21 days, 30 days, 45 days, or 60 days. The method described in.
[Item 92] The contacting may cause the plurality of T cells to be exposed to the first drug for about 10 to 90 minutes, 10 to 60 minutes, 10 to 30 minutes, 1 to 30 days, 1 to 21 days, 1 to 21 days. Incubating or culturing for 14 days, 1-7 days, 1-5 days, 1-3 days, 21-30 days, 14-30 days, 7-30 days, 5-30 days, or 3-30 days , the method according to item 87 or 88.
[Item 93] The method according to any of items 87 to 92, wherein the agent is linked to a solid surface (eg, a bead).
[Item 94] The method according to any one of items 87 to 93, wherein the drug is an antibody, a functional fragment thereof, or a functional variant thereof.
[Item 95] The antibody or functional fragment thereof is a full-length antibody, Fab, (Fab)2, (Fab')2, Fv, (Fv)2, scFv, diabody, triabody, minibody, scFv-Fc fusions, cross-Mabs, tandem diabodies (TandAbs), duobodies, strand exchange engineered domain bodies (SEEDbodies), dual affinity retargeting molecules (DARTs), or dual variable domain immunoglobulins or (DVDs). , the method described in item 94.
[Item 96] The method according to item 94 or 95, wherein the antibody, functional fragment thereof, or functional variant thereof is an anti-idiotypic antibody domain.

Claims (33)

1. A method for reducing an immune response or an excessive immune response induced by an adoptive T cell composition in a subject in need thereof, comprising: a composition comprising a first agent comprising a domain that specifically binds to a T cell receptor beta variable chain (TCRβV) region, the first agent being used in combination with an adoptive T cell composition comprising a plurality of T cells expressing an αβ T cell receptor (TCR) comprising a T cell receptor beta variable chain (TCRβV) region , the method comprising :
(a) administering the adoptive T cell composition to the subject;
(b) administering the first agent to the subject;
wherein the first agent is administered in an amount sufficient to reduce an immune response or an excessive immune response induced by the adoptive T cell therapy in the subject; and
The composition comprises a first agent in an effective amount to result in an increased proliferation rate of the plurality of T cells compared to the plurality of T cells in the absence of the first agent. The composition of claim 1, wherein the reduction is determined by measuring the level of a cytokine or chemokine in a sample from the subject after administration of the first agent, and the reduction is in comparison to the level of the cytokine or chemokine in a sample from the subject before administration of the first agent to the subject and after administration of the adoptive T cell composition . 1. For use in a method of treating cancer in a subject in need thereof, the method comprising: a composition comprising a first agent comprising a domain that specifically binds to a T cell receptor beta variable chain (TCRβV) region, the first agent being used in combination with an adoptive T cell composition comprising a plurality of T cells expressing an αβ T cell receptor (TCR) comprising a T cell receptor beta variable chain (TCRβV) region.
(a) administering the adoptive T cell composition to the subject;
(b) administering the first agent to the subject;
wherein the composition comprises the first agent in an effective amount to result in an increased proliferation rate of the plurality of T cells compared to the plurality of T cells in the absence of the first agent. the first agent is administered in an amount that reduces an immune response or an excessive immune response induced by the adoptive T cell composition in the subject;
The composition of claim 3, wherein the reduction is determined by measuring the level of a cytokine or chemokine in a sample from the subject after administration of the first agent, and the reduction is in comparison to the level of a cytokine or chemokine in a control sample from a subject administered the adoptive T cell composition in the absence of the first agent. 5. The composition of claim 3 or 4 , wherein the method comprises:
(a) administering to the subject another composition comprising the adoptive T cell composition ;
(b) administering to the subject the composition comprising the first agent. 6. The composition of claim 5, wherein the another composition comprises 0.1-10.0 x ¹⁰ T cells/kg of the subject's body weight, 0.1-9.0 x ¹⁰ T cells/kg of the subject's body weight, 0.1-8.0 x ¹⁰ T cells/kg of the subject's body weight, 0.1-7.0 x ¹⁰ T cells/kg of the subject's body weight, 0.1-6.0 x ¹⁰ T cells/kg of the subject's body weight, 0.1-5.0 x ¹⁰ T cells/kg of the subject's body weight, 0.1-4.0 x ¹⁰ T cells/kg of the subject's body weight, 0.1-3.0 x ¹⁰ T cells/kg of the subject's body weight, 0.1-2.0 x ¹⁰ T cells/kg of the subject's body weight, or 0.1-1.0 x ¹⁰ T cells/ kg of the subject's body weight. The additional composition is administered at a concentration of 2×10 per kg of the subject's body weight. ⁶ The composition of claim 6 comprising T cells. 8. The composition of any one of claims ⁵ to 7, wherein the another composition comprises 0.1-10x10 T cells, 0.1-9x10 T cells, ^0.1-8x10 T ^cells , ^0.1-7x10 T cells , ^0.1-6x10 T ^{cells, 0.1-5x10 T cells, 0.1-4x10 T cells} , ^0.1-3x10 T cells, ^0.1-2x10 T cells, or 0.1-1x10 T cells. The other composition is 2×10 ⁸ The composition of claim 8 comprising T cells. The composition of any one of claims 1 to 9, wherein the subject is not administered a conditioning regimen comprising at least one lymphodepleting agent. The at least one lymphodepleting agent is selected from the group consisting of cyclophosphamide, fludarabine, mechlorethamine, chlorambucil, melphalan, ifosfamide, thiotepa, hexamethylmelamine, busulfan, nitrosourea, platinum, methotrexate, azathioprine, mercaptopurine, procarbazine, dacarbazine, temozolomide, carmustine, lomustine, streptozocin, fluorouracil, dactinomycin, anthracyclines, mitomycin C, bleomycin, mithramycin, mycophenolate mofetil, rapamycin, cyclosporine, deoxyspergualin, soluble The composition according to claim 10, which is an anti-thymocyte globulin antibody, an anti-CD154 antibody, an anti-CD40 antibody, an anti-CD20 antibody, an anti-IL-6R antibody, an anti-IL-6 antibody, an anti-IL-2R antibody, an anti-CXCR3 antibody, an anti-ICOS antibody, an anti-OX40 antibody, or an anti-CD122 antibody, an anti-C5 antibody, an abatacept, a belatacept, a sirolimus, an everolimus, acrolimus, a daclizumab, a basiliximab, an infliximab, an eculizumab, a rituximab, an alemtuzumab, a tocilizumab, a sarilumab, or an olokizumab. The composition of any one of claims 1-11, wherein the first agent is administered to the subject before, simultaneously with, or after the adoptive T cell composition is administered to the subject. The composition according to any one of claims 1 to 12, wherein the subject has cancer. (i) the cancer is a hematological malignancy;
(ii) the cancer is a solid tumor;
(iii) the cancer is bladder cancer, epithelial cancer, bone cancer, brain cancer, breast cancer, esophageal cancer, gastrointestinal cancer, liver cancer, lung cancer, ovarian cancer, prostate cancer, sarcoma, stomach cancer, thyroid cancer, acute lymphocytic cancer, alveolar rhabdomyosarcoma, anal canal, rectal cancer, eye cancer, cervical cancer, gallbladder cancer, pleural cancer, oral cancer, vulvar cancer, colon cancer, cervical cancer, fibrosarcoma, gastrointestinal carcinoid tumor, renal cancer, mesothelioma, mast cell tumor, melanoma, nasopharyngeal cancer, pancreatic cancer, peritoneal cancer, renal cancer, skin cancer, small intestine cancer, stomach cancer, or testicular cancer;
(iv) the cancer is leukemia, myeloma, or lymphoma; or (v) the cancer is acute lymphocytic leukemia, acute myeloid leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or multiple myeloma.
The composition of claim 13 . The composition of any one of claims 1 to 14 , wherein the plurality of T cells comprises an exogenous receptor. 16. The composition of claim 15 , wherein the exogenous cell receptor is a chimeric antigen receptor (CAR) or an exogenous T cell receptor (TCR). The composition of claim 16, wherein the chimeric antigen receptor (CAR) or chimeric T cell receptor (TCR) comprises an antigen-binding region that specifically binds to a tumor-associated antigen. The antigen-binding region is selected from the group consisting of CD19, CD123, CD22, CD30, CD171, CS-1, C-type lectin-like molecule-1, CD33, CISH, epidermal growth factor receptor variant III (EGFRvIII), ganglioside G2 (GD2), ganglioside GD3, TNF receptor family member B cell maturation (BCMA), Tn antigen (Tn Ag) or (GalNAcα-Ser/Thr)), prostate-specific membrane antigen (PSMA), receptor tyrosine kinase-like orphan receptor 1 (ROR1), Fms-like tyrosine kinase 3 (FLT3), tumor-associated glycoprotein 72 (TAG72), CD38, CD44v6, carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EPCAM), B7H3 (CD276), KIT (CD117), interleukin-13 receptor subunit alpha-2, mesothelin, interleukin-11 receptor alpha IL-11Ra, prostate stem cell antigen (PSCA), protease serine 21, vascular endothelial growth factor receptor 2 (VEGFR2), Lewis (Y) antigen, CD24, platelet-derived growth factor receptor beta (PDGFR-beta), stage-specific embryonic antigen-4 (SSEA-4), CD20, folate receptor alpha, receptor tyrosine-protein kinase ERBB2 (Her2/neu), mucin 1, cell surface associated (MUC1), epidermal growth factor receptor (EGFR), neural cell adhesion molecule (NCAM), prostaglandin E (prostaglandin F) and serotype 1 (serotype 2). The oncogene fusion protein consists of the oncogene fusion protein α, prostatic acid phosphatase (PAP), elongation factor 2 mutated (ELF2M), ephrinB2, fibroblast activation protein alpha (FAP), insulin-like growth factor 1 receptor (IGF-I receptor), carbonic anhydrase IX (CAIX), proteasome (prosome, macropain) subunit, beta, 9 (LMP2), glycoprotein 100 (gp100), breakpoint cluster region (BCR), and Abelson murine leukemia viral oncogene homolog 1 (Abl). fusion protein (bcr-abl), tyrosinase, ephrin type A receptor 2 (EphA2), fucosyl GM1, sialyl Lewis adhesion molecule (sLe), ganglioside GM3, transglutaminase 5 (TGS5), high molecular weight melanoma-associated antigen (HMWMAA), o-acetyl-GD2 ganglioside (OAcGD2), folate receptor beta, tumor endothelial marker 1 (TEM1/CD248), tumor endothelial marker 7-related (TEM7R), claudin 6 (CLDN6), thyrotropin receptor (TSR), HR), G protein-coupled receptor class C group 5, member D (GPRC5D), chromosome X open reading frame 61 (CXORF61), CD97, CD179a, anaplastic lymphoma kinase (ALK), polysialic acid, placenta specific 1 (PLAC1), hexasaccharide moiety of globo H glycoceramide (GloboH), mammary differentiation antigen (NY-BR-1), uroplakin 2 (UPK2), hepatitis A virus cellular receptor 1 (HAVCR1), adrenergic receptor beta 3 (ADRB3), pannexin 3 (PANX3), G protein-coupled receptor 20 (GPR20), lymphocyte antigen 6 complex, locus K9 (LY6K), olfactory receptor 51E2 (OR51E2), TCR gamma alternative reading frame protein (TARP), Wilms tumor protein (WT1), cancer/testis antigen 1 (NY-ESO-1), cancer/testis antigen 2 (LAGE-1a), melanoma-associated antigen 1 (MAGE-A1), ETS translocation variant gene 6 located on chromosome 12p (ETV6-AML), sperm protein 17 (SP A17), X antigen family, member 1A (XAGE1), angiopoietin-binding cell surface receptor 2 (Tie2), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen 2 (MAD-CT-2), Fos-related antigen 1, tumor protein p53 (p53), p53 mutant, prostein, survivin, telomerase, prostate cancer tumor antigen-1, melanoma antigen 1 recognized by T cells, rat sarcoma (Ras) mutant, human telomerase reverse transcriptase (hTERT), sarcoma translocation breakpoints, apo Melanoma inhibitor of ptosis (ML-IAP), ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene), N-acetylglucosaminyltransferase V (NA17), paired box protein Pax-3 (PAX3), androgen receptor, cyclin B1, v-myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (MYCN), Ras homolog family member C (RhoC), tyrosinase-related protein 2 (TRP-2), cytochrome P450 1B1 (CYP1B1), CCCTC-binding factor (zinc finger protein)-like, T-cell-recognized squamous cell carcinoma antigen 3 (SART3), paired box protein Pax-5 (PAX5), proacrosin-binding protein sp32 (OY-TES1), lymphocyte-specific protein tyrosine kinase (LCK), A-kinase anchoring protein 4 (AKAP-4), synovial sarcoma, X-breakpoint 2 (SSX2), receptor for advanced glycation end products (RAGE-1), renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), legumain, human papillomavirus E6 (HPV E6), human papillomavirus E7 (HPV E7), intestinal carboxylesterase, heat shock protein 70-2 mutant (mutated) 18. The composition of claim 17, which specifically binds to a CD49, CD50, CD60, CD70-2, CD79a, CD79b, CD72, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), Fc fragment of the IgA receptor (FCAR or CD89), leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), CD300 molecule-like family member f (CD300LF), C-type lectin domain family 12 member A (CLEC12A), bone marrow stromal cell antigen 2 (BST2), EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2), lymphocyte antigen 75 (LY75), glypican 3 (GPC3), Fc receptor-like 5 (FCRL5), or immunoglobulin lambda-like polypeptide 1 (IGLL1) antigen. The composition of any one of claims 1 to 18 , wherein the plurality of T cells is allogeneic or autologous to the subject. The composition according to any one of claims 1 to 19, wherein the first agent is an antibody, a functional fragment thereof, or a functional variant thereof. 21. The composition of claim 20, wherein the antibody, functional fragment thereof or functional variant thereof comprises a full length antibody, Fab, (Fab)2, (Fab')2, Fv, (Fv)2, scFv, diabody, triabody, minibody, scFv-Fc fusion, crossMab, tandem diabody (TandAb), duobody, strand-swap engineered domain body (SEEDbody), dual affinity retargeting molecule (DART), or dual variable domain immunoglobulin or (DVD). 1. A composition comprising a first agent comprising a domain that specifically binds to a T cell receptor beta variable chain (TCRβV) region, used in combination with an adoptive T cell composition comprising a plurality of T cells expressing an αβ T cell receptor (TCR) comprising a T cell receptor beta variable chain (TCRβV) region, for use in a method of reducing cytokine or chemokine release induced by the adoptive T cell composition in a subject in need thereof, the method comprising:
(a) measuring a first level of a cytokine or chemokine in a first sample from the subject prior to administering the adoptive T cell composition to the subject;
(b) administering the adoptive T cell composition to the subject;
(c) measuring a second level of said cytokine or chemokine in a second sample from said subject after administering said adoptive T cell composition to said subject;
(d) comparing the first level with the second level to determine whether the subject has or is at risk for developing excessive cytokine or chemokine release induced by the adoptive T cell composition ;
(e) if the subject is determined to have or be at risk for developing the excessive cytokine or chemokine release, administering a first agent to the subject, wherein the excessive cytokine or chemokine release is ameliorated by the first agent, wherein the composition comprises the first agent in an effective amount to result in an increased proliferation rate of the plurality of T cells compared to the plurality of T cells in the absence of the first agent . The composition of claim 22, wherein the excessive cytokine or chemokine release is associated with an excessive immune response induced by the adoptive T cell composition . 24. The composition of any one of claims 1 to 23, wherein the subject has or is at risk of developing cytokine release syndrome, macrophage activation syndrome, neurotoxicity, or tumor lysis syndrome associated with the immune response or the excessive immune response induced by the adoptive T cell composition. The object is
(i) hemophagocytic lymphohistiocytosis (HLH), fever, nausea, vomiting, chills, hypotension, tachycardia, arrhythmia, cardiomyopathy, acute heart failure, asthenia, headache, rash, dyspnea, encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, hallucinations, cerebral edema, hepatomegaly, hypofibrinogenemia, liver failure, diarrhea, edema, rigidity, arthralgia, myalgia, acute renal failure, splenomegaly, respiratory failure, pulmonary edema, hypoxia, capillary leak syndrome, macrophage activation syndrome, or tachypnea associated with cytokine release syndrome;
(ii) encephalopathy, aphasia, tremor, ataxia, hemiparesis, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, or cerebral edema associated with cytokine release syndrome ;
25. The composition of claim 24, wherein the patient has or is at risk of developing: (iii) fever, headache, lymphadenopathy, hepatosplenomegaly, coagulopathy, rash, tachycardia, arrhythmia, cardiomyopathy, lethargy, pancytopenia, liver dysfunction, disseminated intravascular coagulation, hypofibrinogenemia, hyperferritinemia, or hypertriglyceridemia associated with macrophage activation syndrome; or (iv) nausea, vomiting, diarrhea, muscle cramps, muscle spasms, weakness, numbness, tingling, fatigue, lethargy, decreased urination, encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, cerebral edema, or hallucinations associated with tumor lysis syndrome . The composition,
(i) in a subject, hemophagocytic lymphohistiocytosis (HLH), fever, nausea, vomiting, chills, hypotension, tachycardia, arrhythmia, cardiomyopathy, acute heart failure, asthenia, headache, rash, dyspnea, encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, hallucinations, cerebral edema, hepatomegaly, hypofibrinogenemia, liver failure, diarrhea, edema, stiffness, arthralgia, myalgia, acute renal failure, splenomegaly, respiratory failure, pulmonary edema, hypoxia, capillary leak syndrome, macrophage activation syndrome, or tachypnea associated with cytokine release syndrome;
(ii) encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, or cerebral edema associated with cytokine release syndrome in a subject;
26. The composition of claim 25, comprising an effective amount of a first agent to ameliorate at least one of: (iii) fever, headache, lymphadenopathy, hepatosplenomegaly, coagulopathy, rash, tachycardia, arrhythmia, cardiomyopathy, lethargy, pancytopenia, liver dysfunction, disseminated intravascular coagulation, hypofibrinogenemia, hyperferritinemia, or hypertriglyceridemia associated with macrophage activation syndrome in a subject; or (iv) nausea, vomiting, diarrhea, muscle cramps, muscle spasms, weakness, numbness, tingling, fatigue, lethargy, decreased urination, encephalopathy, aphasia, tremor, ataxia, hemiplegia, paralysis, dysmetria, seizures, motor weakness, loss of consciousness, cerebral edema, or hallucinations associated with tumor lysis syndrome in a subject. The composition of any one of claims 1 to 26, wherein the plurality of T cells is expanded ex vivo by contacting the plurality of T cells with an agent that includes a domain that specifically binds to a T cell receptor beta variable chain (TCRβV) region. The composition of claim 27 , wherein the agent is an antibody, a functional fragment thereof, or a functional variant thereof. 29. The composition of claim 28, wherein the antibody, functional fragment thereof or functional variant thereof comprises a full length antibody, Fab, (Fab)2, (Fab')2, Fv, (Fv)2, scFv, diabody, triabody, minibody, scFv-Fc fusion, crossMab, tandem diabody (TandAb), duobody, strand-swap engineered domain body (SEEDbody), dual affinity retargeting molecule (DART), or dual variable domain immunoglobulin or (DVD). The composition of claim 29 , wherein the antibody, functional fragment thereof, or functional variant thereof is an anti-idiotype antibody domain. The TCRβ V region is selected from the group consisting of TCRβ V6 subfamily, TCRβ V10 subfamily, TCRβ V12 subfamily, TCRβ V5 subfamily, TCRβ V7 subfamily, TCRβ V11 subfamily, TCRβ V14 subfamily, TCRβ V16 subfamily, TCRβ V18 subfamily, TCRβ V9 subfamily, TCRβ V13 subfamily, TCRβ V4 subfamily, TCRβ V3 subfamily, TCRβ V2 subfamily, TCRβ V15 subfamily, TCRβ V30 subfamily, TCRβ V19 subfamily, TCRβ V27 subfamily, TCRβ V28 subfamily, TCRβ V24 subfamily, TCRβ V20 subfamily, TCRβ V25 subfamily, and TCRβ. The composition according to any one of claims 1 to 30 , which is a TCRβV region of a TCRβV belonging to the V29 subfamily. The plurality of T cells express an αβ T cell receptor (TCR) comprising a T cell receptor beta variable chain (TCRβV) region, the TCRβV region being selected from the group consisting of TCRβ V6 subfamily, TCRβ V10 subfamily, TCRβ V12 subfamily, TCRβ V5 subfamily, TCRβ V7 subfamily, TCRβ V11 subfamily, TCRβ V14 subfamily, TCRβ V16 subfamily, TCRβ V18 subfamily, TCRβ V9 subfamily, TCRβ V13 subfamily, TCRβ V4 subfamily, TCRβ V3 subfamily, TCRβ V2 subfamily, TCRβ V15 subfamily, TCRβ V30 subfamily, TCRβ V19 subfamily, TCRβ V27 subfamily, TCRβ V28 subfamily, TCRβ V30 subfamily, TCRβ V31 subfamily, TCRβ V32 subfamily, TCRβ V33 subfamily, TCRβ V34 subfamily, TCRβ V35 subfamily, TCRβ V36 subfamily, TCRβ V37 subfamily, TCRβ V38 subfamily, TCRβ V39 subfamily, TCRβ V40 subfamily, TCRβ V41 subfamily, TCRβ V42 subfamily, TCRβ V43 subfamily, TCRβ V44 subfamily, TCRβ V45 subfamily, TCRβ V46 subfamily, TCRβ V47 subfamily, TCRβ V48 subfamily, TCRβ V49 subfamily, TCRβ V50 subfamily, TCRβ V51 subfamily, TCRβ V52 subfamily, TCRβ V53 subfamily, TCRβ V54 subfamily, TCRβ V55 subfamily, TCRβ V56 subfamily, TCRβ V57 subfamily, TCRβ V58 subfamily, TCRβ V59 subfamily, TCRβ V60 subfamily, TCRβ V61 subfamily, TCRβ V62 subfamily, TCRβ The composition according to any one of claims 1 to 31 , which is a TCRβV region of a TCRβV belonging to the V24 subfamily, the TCRβ V20 subfamily, the TCRβ V25 subfamily, or the TCRβ V29 subfamily. The cytokine or chemokine is IL-6, IFNγ, TNFα, IFNα, I
33. The composition of any one of claims 2 and 4 to 32, wherein the IL-1β is IL-8, IL-10, IL-2, IL-4, IL-5, IL-7, IL-10, IL-13, IL- 15 , IL-1RA, sIL1RI, sIL1RII, sIL2Rα, sgp130, sIL6R, MCP1, MIP1α, MIP1β, MIG, GCSF, IP10, sTNFRI, sTNFRII, HGF, VEGF, sCD30, or GM-CSF.