T-cell therapy in patients who have previously undergone stem cell transplantation

Abstract

Provided herein is the use of a T cell, e.g., a chimeric antigen receptor (CAR) T cell, to treat a tumor or cancer (e.g., a B cell-related cancer, e.g., multiple myeloma), where the subject being treated has previously undergone a stem cell transplant.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 176,192, filed April 16, 2021, entitled "CELL THERAPY IN PATIENTS WHO HAVE HAD PRIOR STEM CELL TRANSPLANT," the contents of which are incorporated herein by reference in their entirety.

[0002] Incorporation by Reference of Sequence Listing This application is filed with a Sequence Listing in electronic format. The Sequence Listing is provided as a file titled 683772002140SeqList.txt, created on April 15, 2022, and is 418,478 bytes in size. The information in the electronic format of the Sequence Listing is incorporated by reference in its entirety.

[0003] Technical Field The disclosures provided herein relate to methods for treating tumors or cancers (e.g., B-cell-related cancers, e.g., multiple myeloma). More particularly, the disclosure relates to improved methods for treating tumors or cancers (e.g., B-cell-related cancers, e.g., multiple myeloma) using immune effector cells (e.g., T cells), wherein the subject being treated has previously undergone stem cell transplantation. The disclosure also relates to methods for treating tumors or cancers (e.g., B-cell-related cancers, e.g., multiple myeloma) using chimeric antigen receptors (CARs) comprising antibodies or antigen-binding fragments thereof (e.g., anti-BCMA antibodies or antigen-binding fragments thereof), and immune effector cells (e.g., T cells) genetically engineered to express these CARs. The disclosure also relates to methods for producing T cells and CARs comprising antibodies or antigen-binding fragments thereof (e.g., anti-BCMA antibodies or antigen-binding fragments thereof) for treating tumors or cancers (e.g., B-cell-related cancers, e.g., multiple myeloma). [Background technology]

[0004] Currently, many options for approaching cancer treatment are available, such as traditional chemotherapy approaches, as well as immunotherapy (for example, chimeric antigen receptor CAR) T cell therapy.In certain cases, the use of a certain therapy or procedure may cause subsequent administration to be suboptimal.Therefore, when cancer therapy, for example, T cell therapy, for example, CAR-T therapy, is administered to patients, for example, when it is administered sequentially with other cancer therapy or procedures related to cancer therapy, it is necessary to optimize the administration of this therapy. Summary of the Invention

[0005] The present disclosure generally provides improved methods of treating tumors or cancers, such as B-cell related cancers, eg, multiple myeloma. [Brief explanation of the drawings]

[0006] [Figure 1] FIG. 1 shows a schematic diagram of the B-cell maturation antigen (BCMA) CAR construct (anti-BCMA02 CAR). [Figure 2] Figure 2 shows the phenotype of cells collected during leukapheresis from patients with relapsed and refractory multiple myeloma. Results are grouped based on the length of time between the patient's prior autologous stem cell transplant (ASCT) therapy and leukapheresis. Leukapheresis samples were collected for the product of anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. [Figure 3] Figure 3 shows an cumulative local effect (ALE) plot of a trained random forest model showing the probability of a patient's disease progression after CAR T-cell therapy based on the length of time between the patient's prior ASCT therapy and leukapheresis. [Figure 4]Figure 4 shows an cumulative local effect (ALE) plot of a trained random forest model showing the time to recovery of patients from grade 3 or higher thrombocytopenia after CAR T-cell therapy based on the length of time between the patient's prior ASCT therapy and leukapheresis. [Figure 5] Figure 5 shows the cumulative local effect (ALE) plot of a trained random forest model showing the effect on the phenotype of peripheral blood mononuclear cells (PBMCs) collected during leukapheresis based on the length of time between a patient's prior ASCT therapy and leukapheresis. DETAILED DESCRIPTION OF THE INVENTION

[0007]

[0010] In one aspect, provided herein is a method for treating a tumor or cancer in a subject in need thereof, the method comprising: (a) administering a stem cell transplant (SCT) to the subject; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 9 months after step (a); (c) producing T cells from the PBMCs; and then (d) administering the produced T cells to the subject. In a specific embodiment, step (b) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a). In a specific embodiment, step (b) is performed at least about 12 months after step (a).

[0008] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia, or leukemia) (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, acute myeloid leukemia (AML), lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) ), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T-lymphocytic leukemia / lymphoma, extranodal NK / T-lymphocytic lymphoma, nasal type, enteropathy-type T-lymphocytic lymphoma, hepatosplenic T-lymphocytic lymphoma, blastic NK-cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T-lymphocytic lymphoma, peripheral T-lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In specific embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.In a specific embodiment, the cancer is multiple myeloma. In a specific embodiment, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In a specific embodiment, the multiple myeloma is high-risk multiple myeloma. In a specific embodiment, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In a specific embodiment, the multiple myeloma is not Revised International Staging Classification (R-ISS) stage III disease. In a specific embodiment, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0009] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0010] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0011] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0012] In certain embodiments, the subject is a human.

[0013] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0014] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0015] In another aspect, provided herein is a method of treating a tumor or cancer in a subject in need thereof, comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells from the PBMCs; and then (c) administering the produced T cells to the subject, wherein prior to step (a), the subject has undergone a prior stem cell transplant (SCT) as part of a cancer treatment. In a specific embodiment, the subject has undergone a prior stem cell transplant (SCT) at least about 9 months prior to step (a). In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to step (a). In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 12 months prior to step (a).

[0016] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0017] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0018] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0019] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0020] In certain embodiments, the subject is a human.

[0021] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0022] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0023] In another aspect, a method of treating a tumor or cancer in a subject in need thereof comprises: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells from the PBMCs; and then (c) administering the produced T cells to the subject, wherein the subject has previously undergone stem cell transplantation (SCT) as part of a treatment for the tumor or cancer; and step (a) is performed at least about 9 months after the subject has undergone the stem cell transplantation (SCT). In certain embodiments, step (a) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has undergone the stem cell transplantation (SCT). In a specific embodiment, step (a) is performed at least 12 months after the subject has undergone the stem cell transplantation.

[0024] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0025] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0026] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0027] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0028] In certain embodiments, the subject is a human.

[0029] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0030] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0031] In another aspect, provided herein is a method for treating a tumor or cancer in a subject in need thereof, wherein the subject has received a stem cell transplant (SCT), the method comprising: (a) determining that the subject has not received a stem cell transplant (SCT) for less than about 9 months prior to the determining step; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (c) producing T cells from the PBMCs; and then (d) administering the produced T cells to the subject. In certain embodiments, in step (a), the subject has not received a stem cell transplant (SCT) for less than about 10 months, less than about 11 months, less than about 12 months, less than about 13 months, less than about 14 months, less than about 15 months, less than about 16 months, less than about 17 months, or less than about 18 months prior to the determining step. In certain embodiments, in step (a), the subject has not received a stem cell transplant (SCT) for less than about 12 months prior to the determining step.

[0032] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory myeloma.

[0033] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0034] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0035] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0036] In certain embodiments, the subject is a human.

[0037] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0038] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0039] In another aspect, provided herein is a method for treating tumor or cancer in a subject in need thereof, wherein the subject has undergone stem cell transplantation (SCT), the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells from the PBMCs; and then (c) administering the produced T cells to the subject, wherein at the time of isolation, the subject has been determined to have undergone stem cell transplantation (SCT) at least about 9 months ago. In certain embodiments, the subject has been determined to have undergone stem cell transplantation (SCT) at least about 10 months ago, at least about 11 months ago, at least about 12 months ago, at least about 13 months ago, at least about 14 months ago, at least about 15 months ago, at least about 16 months ago, at least about 17 months ago, or at least about 18 months ago. In a specific embodiment, the subject has been determined to have undergone stem cell transplantation (SCT) at least about 12 months ago.

[0040] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0041] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0042] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0043] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0044] In certain embodiments, the subject is a human.

[0045] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0046] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0047] In another aspect, provided herein is a method of treating a tumor or cancer in a subject in need thereof, wherein the subject has undergone stem cell transplantation (SCT), the method comprising administering to the subject T cells prepared from peripheral blood mononuclear cells (PBMCs) isolated from the patient, wherein, at the time the PBMCs are isolated, the subject last underwent a stem cell transplant (SCT) at least about 9 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent a stem cell transplant at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to the time the PBMCs are isolated. In certain embodiments, the subject underwent a stem cell transplant at least about 12 months prior to the time the PBMCs are isolated.

[0048] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0049] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0050] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0051] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0052] In certain embodiments, the subject is a human.

[0053] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0054] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0055] In another aspect, provided herein is a method for treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, the method comprising: (a) administering stem cell transplantation (SCT) to the subject; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 9 months after step (a); (c) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (d) administering the BCMA CAR T cells to the subject. In certain embodiments, step (b) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a) of administering stem cell transplantation (SCT) to the subject. In certain embodiments, step (b) is performed at least about 12 months after step (a) of administering stem cell transplantation (SCT) to the subject.

[0056] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0057] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In a specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0058] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0059] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0060] In certain embodiments, the subject is a human.

[0061] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecabtagene vicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are ciltacabtagene autoleucel cells. In a specific embodiment, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0062] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0063] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0064] In another aspect, provided herein is a method of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (c) administering the BCMA CAR T cells to the subject, wherein prior to step (a), the subject has undergone a prior stem cell transplant (SCT) as part of a treatment for cancer. In certain embodiments, the subject has undergone a prior stem cell transplant at least about 9 months prior to step (a). In certain embodiments, the subject has undergone a prior stem cell transplant at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to step (a). In certain embodiments, the subject has undergone a prior stem cell transplant at least about 12 months prior to step (a).

[0065] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0066] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In a specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0067] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0068] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0069] In certain embodiments, the subject is a human.

[0070] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0071] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0072] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0073]

[0009] In another aspect, provided herein are methods of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need thereof, the methods comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and (c) administering the BCMA CAR T cells to the subject, wherein the subject has previously undergone stem cell transplantation (SCT) as part of a treatment for cancer, and step (a) is performed at least about 9 months after the subject has undergone the stem cell transplantation (SCT). In certain embodiments, step (a) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has undergone the stem cell transplantation (SCT). In certain embodiments, step (a) is performed at least about 12 months after the subject has undergone stem cell transplantation (SCT).

[0074] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0075] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0076] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0077] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0078] In certain embodiments, the subject is a human.

[0079] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0080] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0081] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0082] In another aspect, provided herein is a method for treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, wherein the subject has received stem cell transplantation (SCT) as part of the cancer treatment, the method comprising: (a) determining that the subject has not received stem cell transplantation (SCT) for less than about 9 months prior to the determining step; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject, the isolating step being performed at least 9 months after the stem cell transplantation (SCT) has been administered to the subject; (c) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (d) administering the BCMA CAR T cells to the subject. In certain embodiments, in step (a), the subject has not received stem cell transplantation (SCT) for less than about 10 months, less than about 11 months, less than about 12 months, less than about 13 months, or less than about 14 months prior to the determining step. In certain embodiments, in step (a), the subject has not received a stem cell transplant (SCT) in less than about 12 months prior to the determining step.

[0083] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0084] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0085] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0086] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0087] In certain embodiments, the subject is a human.

[0088] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0089] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0090] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0091] In another aspect, provided herein is a method for treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need thereof, wherein the subject has received a stem cell transplant (SCT), the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (c) administering the BCMA CAR T cells to the subject, wherein at the time of isolation, the subject has been determined to have received a stem cell transplant (SCT) at least about 9 months prior. In certain embodiments, the subject has been determined to have received a stem cell transplant at least about 10 months prior, at least about 11 months prior, at least about 12 months prior, at least about 13 months prior, at least about 14 months prior, at least about 15 months prior, at least about 16 months prior, at least about 17 months prior, or at least about 18 months prior. In certain embodiments, the subject has been determined to have received a stem cell transplant at least about 12 months prior.

[0092] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0093] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0094] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0095] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0096] In certain embodiments, the subject is a human.

[0097] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0098] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0099] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0100] In another aspect, provided herein is a method of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need thereof, wherein the subject has undergone stem cell transplantation (SCT), the method comprising administering to the subject chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) prepared from peripheral blood mononuclear cells (PBMCs) isolated from the patient, wherein, at the time the PBMCs are isolated, the subject last underwent a stem cell transplant (SCT) at least about 9 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent a stem cell transplant at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent a stem cell transplant at least about 12 months prior to the time the PBMCs are isolated.

[0101] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0102] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0103] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0104] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0105] In certain embodiments, the subject is a human.

[0106] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, e.g., the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0107] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0108] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0109]

[0010] In another aspect, provided herein is a method of shortening the time to recovery from thrombocytopenia following T cell therapy in a subject, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells from the PBMCs; and then (c) administering the produced T cells to the subject, wherein the subject has undergone a prior stem cell transplant (SCT) at least about 9 months prior to step (a). In some embodiments, the subject has undergone a prior SCT at least about 12 months prior to step (a).

[0110] In another aspect, provided herein is a method of producing T cells from a subject, the method comprising: (a) administering stem cell transplantation (SCT) to the subject as part of a tumor or cancer treatment; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 9 months after step (a); and then (c) producing T cells from the PBMCs. In certain embodiments, step (b) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a). In certain embodiments, step (b) is performed at least about 12 months after step (a).

[0111] In certain embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, striated muscle tumor, sarcoma ... Sarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphoprolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer may be lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or multiple myeloma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is a non-Hodgkin's lymphoma, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0112] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0113] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0114] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0115] In certain embodiments, the subject is a human.

[0116] In certain embodiments, prior to administering the CAR T cells to the subject, the subject undergoes an apheresis procedure, such as a leukapheresis procedure, to collect PBMCs for the manufacture of CAR T cells.

[0117] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0118] In another aspect, provided herein is a method of producing T cells from a subject, comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; and then (b) producing T cells from the PBMCs, wherein at least 9 months prior to step (a), the subject has undergone a prior stem cell transplant (SCT) as part of a treatment for a tumor or cancer. In certain embodiments, the subject has undergone a prior stem cell transplant at least about 9 months prior to step (a). In certain embodiments, the subject has undergone a prior stem cell transplant at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to step (a). In certain embodiments, the subject has undergone a prior stem cell transplant at least about 12 months prior to step (a).

[0119] In certain embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, striated muscle tumor, sarcoma ... Sarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphoprolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer may be lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or multiple myeloma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is a non-Hodgkin's lymphoma, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0120] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0121] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0122] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0123] In certain embodiments, the subject is a human.

[0124] In certain embodiments, prior to administering the CAR T cells to the subject, the subject undergoes an apheresis procedure, such as a leukapheresis procedure, to collect PBMCs for the manufacture of CAR T cells.

[0125] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0126] In another aspect, provided herein is a method of producing T cells from a subject, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; and then (b) producing T cells from the PBMCs, wherein the subject has previously undergone stem cell transplantation (SCT) as part of a tumor or cancer treatment; and step (a) is performed at least about 9 months after the subject has undergone stem cell transplantation (SCT). In certain embodiments, step (a) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has undergone stem cell transplantation (SCT). In certain embodiments, step (a) is performed at least about 12 months after the subject has undergone stem cell transplantation (SCT).

[0127] In certain embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, striated muscle tumor, sarcoma ... Sarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphoprolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer may be lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or multiple myeloma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is a non-Hodgkin's lymphoma, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0128] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0129] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0130] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0131] In certain embodiments, the subject is a human.

[0132] In certain embodiments, prior to administering the CAR T cells to the subject, the subject undergoes an apheresis procedure, such as a leukapheresis procedure, to collect PBMCs for the manufacture of CAR T cells.

[0133] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0134] In another aspect, provided herein is a method of producing T cells from a subject, wherein the subject has received a stem cell transplant (SCT) as part of treatment for a tumor or cancer, the method comprising: (a) determining that the subject has not received a stem cell transplant (SCT) for less than about 9 months prior to the determining step; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject; and then (c) producing chimeric T cells from the PBMCs. In certain embodiments, in step (a), the subject has not received a stem cell transplant for less than about 10 months, less than about 11 months, less than about 12 months, less than about 13 months, less than about 14 months, less than about 15 months, less than about 16 months, less than about 17 months, or less than about 18 months prior to the determining step. In certain embodiments, in step (a), the subject has not received a stem cell transplant for less than about 12 months prior to the determining step.

[0135] In certain embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, striated muscle tumor, sarcoma ... Sarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphoprolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer may be lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or multiple myeloma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is a non-Hodgkin's lymphoma, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0136] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0137] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0138] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0139] In certain embodiments, the subject is a human.

[0140] In certain embodiments, prior to administering the CAR T cells to the subject, the subject undergoes an apheresis procedure, such as a leukapheresis procedure, to collect PBMCs for the manufacture of CAR T cells.

[0141] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0142] In another aspect, provided herein is a method of producing T cells from a subject, wherein the subject has received a stem cell transplant (SCT) as part of a tumor or cancer treatment, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; and then (b) producing T cells from the PBMCs, wherein at the time of isolation, it has been determined that the subject received a stem cell transplant (SCT) at least about 9 months prior. In certain embodiments, it has been determined that the subject received a stem cell transplant at least about 10 months prior, at least about 11 months prior, at least about 12 months prior, at least about 13 months prior, at least about 14 months prior, at least about 15 months prior, at least about 16 months prior, at least about 17 months prior, or at least about 18 months prior. In certain embodiments, it has been determined that the subject received a stem cell transplant at least about 12 months prior.

[0143] In certain embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, striated muscle tumor, sarcoma ... Sarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphoprolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer may be lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or multiple myeloma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is a non-Hodgkin's lymphoma, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0144] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0145] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0146] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0147] In certain embodiments, the subject is a human.

[0148] In certain embodiments, prior to administering the CAR T cells to the subject, the subject undergoes an apheresis procedure, such as a leukapheresis procedure, to collect PBMCs for the manufacture of CAR T cells.

[0149] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0150]

[0010] In another aspect, provided herein are methods of producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from a subject, the methods comprising: (a) administering a stem cell transplant (SCT) to the subject as part of a treatment for cancer; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 9 months after step (a); and then (c) producing the BCMA CAR T cells from the PBMCs. In certain embodiments, step (b) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a). In certain embodiments, step (b) is performed at least about 12 months after step (a).

[0151] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, which is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0152] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0153] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0154] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0155] In certain embodiments, the subject is a human.

[0156] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0157] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0158] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0159] In another aspect, provided herein is a method of producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from a subject, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; and then (b) producing BCMA CAR T cells from the PBMCs, wherein at least 9 months prior to step (a), the subject has undergone a prior stem cell transplant (SCT) as part of a treatment for cancer. In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 9 months prior to step (a). In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to step (a). In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 12 months prior to step (a).

[0160] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, which is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0161] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0162] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0163] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0164] In certain embodiments, the subject is a human.

[0165] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0166] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0167] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0168] In another aspect, provided herein is a method of producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from a subject, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; and then (b) producing BCMA CAR T cells from the PBMCs, wherein the subject has previously undergone stem cell transplantation (SCT) as part of a treatment for cancer; and step (a) is performed at least about 9 months after the subject has undergone the stem cell transplantation (SCT). In certain embodiments, step (a) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has undergone the stem cell transplantation. In certain embodiments, step (a) is performed at least about 12 months after the subject has undergone the stem cell transplantation.

[0169] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, which is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0170] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0171] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0172] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0173] In certain embodiments, the subject is a human.

[0174] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0175] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0176] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0177] In another aspect, provided herein are methods of producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from a subject, wherein the subject has received a stem cell transplant (SCT) as part of a treatment for cancer, the method comprising: (a) determining that the subject has not received a stem cell transplant (SCT) less than about 9 months prior to the determining step; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject; and then (c) producing the BCMA CAR T cells from the PBMCs. In certain embodiments, step (a) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has received the stem cell transplant. In certain embodiments, step (a) is performed at least about 12 months after the subject has received the stem cell transplant.

[0178] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, which is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0179] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0180] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0181] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0182] In certain embodiments, the subject is a human.

[0183] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0184] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0185] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0186] In another aspect, provided herein is a method of producing chimeric antigen receptor (CAR) T cells (c) against BCMA from a subject, wherein the subject has received a stem cell transplant (SCT) as part of a cancer treatment, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; and then (b) producing BCMA T cells from the PBMCs, wherein at the time of isolation, it has been determined that the subject received a stem cell transplant (SCT) at least about 9 months previously. In certain embodiments, it has been determined that the subject received a stem cell transplant at least about 10 months previously, at least about 11 months previously, at least about 12 months previously, at least about 13 months previously, at least about 14 months previously, at least about 15 months previously, at least about 16 months previously, at least about 17 months previously, or at least about 18 months previously. In certain embodiments, it has been determined that the subject received a stem cell transplant at least about 12 months previously.

[0187] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, which is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0188] In a specific embodiment, the stem cell transplant (SCT) is an autologous stem cell transplant, an allogeneic stem cell transplant, a syngeneic stem cell transplant, or a tandem stem cell transplant. In another specific embodiment, the stem cell transplant is an autologous stem cell transplant. In another specific embodiment, the stem cell transplant is an allogeneic stem cell transplant.

[0189] In certain embodiments, the stem cell transplant (SCT) is a bone marrow transplant, a peripheral blood stem cell transplant, or an umbilical cord blood stem cell transplant.

[0190] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells.

[0191] In certain embodiments, the subject is a human.

[0192] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02scFv. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0193] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0194] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0195] In certain embodiments, producing T cells from PBMCs comprises (a) isolating PBMCs from a leukapheresis sample; and then (b) introducing into the isolated cells a recombinant nucleic acid encoding a chimeric antigen receptor (CAR).

[0196] In certain embodiments, the manufacturing comprises the steps of (a) isolating T cells from a leukapheresis sample; and then (b) introducing into the isolated cells a recombinant nucleic acid encoding a chimeric antigen receptor (CAR).

[0197] In certain embodiments, the introduction is by transduction with a viral vector comprising a recombinant nucleic acid encoding the CAR.

[0198] In certain embodiments, the viral vector partical is a lentiviral vector.

[0199] In certain embodiments, prior to the introducing, the producing further comprises stimulating the composition of T cells with an agent capable of activating T cells.

[0200] In certain embodiments, the agent comprises an anti-CD3 antibody and / or an anti-CD28 antibody.

[0201] In certain embodiments, the manufacturing further comprises expanding the cells into which the recombinant nucleic acid encoding the chimeric antigen receptor (CAR) has been introduced.

[0202] In a specific embodiment, the CAR is an anti-BCMA CAR.

[0203] In certain embodiments, the chimeric antigen receptor (CAR) comprises an extracellular antigen-binding domain that binds BCMA, a transmembrane domain, and an intracellular signaling region.

[0204] In certain embodiments, the intracellular signaling region further comprises a costimulatory signaling domain.

[0205] In certain embodiments, the costimulatory signaling domain comprises the intracellular signaling domain of CD28, 4-1BB, or ICOS, or a signaling portion thereof.

[0206] In certain embodiments, the costimulatory signaling domain is between the transmembrane domain and the cytoplasmic signaling domain of the CD3-zeta (CD3ζ) chain.

[0207] In certain embodiments, the transmembrane domain is or comprises a transmembrane domain from CD28 or CD8, and may be or comprise a transmembrane domain from human CD28 or CD8.

[0208] In certain embodiments, the CAR further comprises an extracellular spacer between the antigen binding domain and the transmembrane domain.

[0209] In certain embodiments, the spacer is from CD8. In certain embodiments, the spacer is a CD8α hinge.

[0210] In a specific embodiment, the transmembrane domain and spacer are from CD8.

[0211] BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows a schematic diagram of the B-cell maturation antigen (BCMA) CAR construct (anti-BCMA02 CAR). Figure 2 shows the phenotype of cells collected during leukapheresis from patients with relapsed and refractory multiple myeloma. Results are grouped based on the length of time between the patient's prior autologous stem cell transplant (ASCT) therapy and leukapheresis. Leukapheresis samples were collected for the product of anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. Figure 3 shows an cumulative local effect (ALE) plot of a trained random forest model showing the probability of a patient's disease progression after CAR T-cell therapy based on the length of time between the patient's prior ASCT therapy and leukapheresis. Figure 4 shows an cumulative local effect (ALE) plot of a trained random forest model showing the time to recovery of patients from grade 3 or higher thrombocytopenia after CAR T-cell therapy based on the length of time between the patient's prior ASCT therapy and leukapheresis. Figure 5 shows the cumulative local effect (ALE) plot of a trained random forest model showing the effect on the phenotype of peripheral blood mononuclear cells (PBMCs) collected during leukapheresis based on the length of time between a patient's prior ASCT therapy and leukapheresis.

[0212] Brief description of sequence identifiers SEQ ID NOs: 1-3 show the amino acid sequences of exemplary light chain CDR sequences of BCMA CARs contemplated herein.

[0213] SEQ ID NOs: 4-6 show the amino acid sequences of exemplary heavy chain CDR sequences of BCMA CARs contemplated herein.

[0214] SEQ ID NO: 7 shows the amino acid sequence of an exemplary light chain sequence of a BCMA CAR contemplated herein.

[0215] SEQ ID NO: 8 shows the amino acid sequence of an exemplary heavy chain sequence of a BCMA CAR contemplated herein.

[0216] SEQ ID NO: 9 shows the amino acid sequence of an exemplary BCMA CAR contemplated herein, with its signal peptide (amino acids 1-21). The amino acid sequence of the mature form of BCMA02 is shown in SEQ ID NO: 37.

[0217] SEQ ID NO: 10 shows a polynucleotide sequence encoding an exemplary BCMA CAR contemplated herein.

[0218] SEQ ID NO: 11 shows the amino acid sequence of human BCMA.

[0219] SEQ ID NOs: 12 to 22 show the amino acid sequences of various linkers.

[0220] SEQ ID NOs: 23 to 35 show the amino acid sequences of the protease cleavage site and the self-cleaving polypeptide cleavage site.

[0221] SEQ ID NO: 36 shows the polynucleotide sequence of an exemplary BCMA CAR-encoding vector. See Table 1.

[0222] SEQ ID NO: 37 shows the amino acid sequence of an exemplary mature BCMA CAR (i.e., without the signal sequence) contemplated herein.

[0223] SEQ ID NO: 38 shows the amino acid sequence of BCMA02 scFv.

[0224] Table 1: Sequence Listing: [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6]

[0225] Detailed Description Methods for treating tumors or cancer using IT cells and methods for producing T cells The disclosures provided herein generally relate to improved methods for treating tumors or cancers (e.g., B-cell-related diseases or cancers, such as multiple myeloma). The disclosures provided herein also relate to methods of manufacturing T cells, e.g., CAR T cells (e.g., CAR T cells directed against BCMA (BCMA CAR T cells)). The term "B-cell-related condition," as used herein, relates to conditions involving inappropriate B-cell activity or B-cell malignancies.

[0226] Certain embodiments presented herein relate to improved adoptive cell therapy of diseases (e.g., tumors or cancers, or B-cell-related diseases or cancers, such as multiple myeloma) using T cells (e.g., genetically modified immune effector cells, e.g., CAR T cells). Genetic approaches offer a promising means to enhance immune recognition and elimination of cancer cells. One promising strategy is to genetically engineer immune effector cells to express chimeric antigen receptors (CARs), which redirect cytotoxicity to cancer cells.

[0227] Improved methods of administering T cell therapy (e.g., CAR T cell therapy) for use in subjects (e.g., patients) who have received a stem cell transplant (SCT) (e.g., in conjunction with (e.g., following) treatment with radiation therapy, chemotherapy, or both) prior to administering the T cell therapy disclosed herein include methods wherein the step of isolating peripheral blood mononuclear cells (PBMCs) from the subject occurs after a period of time after the stem cell transplant is administered to the subject (i.e., a "washout" period). Improved methods of administering T cell therapy (e.g., CAR T cell therapy) for use in subjects who have received a stem cell transplant (e.g., in conjunction with (e.g., following) treatment with radiation therapy, chemotherapy, or both) prior to administering the T cell therapy disclosed herein can be used with genetically modified immune effector cells (e.g., CAR T cells) that can be readily expanded and exhibit long-term persistence in vivo, e.g., genetically modified immune effector cells (e.g., CAR T cells) that reduce impairment of humoral immunity by targeting B cells expressing B-cell maturation antigen (BCMA, also known as CD269 or tumor necrosis factor receptor superfamily, member 17; TNFRSF17). Also disclosed herein are improved methods of producing T cells, e.g., CAR T cells (e.g., BCMA CAR T cells), from PBMCs isolated from patients who have received a stem cell transplant (e.g., in conjunction with (e.g., following) treatment with radiation therapy, chemotherapy, or both).

[0228] BCMA is a member of the tumor necrosis factor receptor superfamily (see, e.g., Thompson et al., J. Exp. Medicine, 192(1): 129-135, 2000, and Mackay et al., Annu. Rev. Immunol, 21: 231-264, 2003). BCMA binds to B-cell activating factor (BAFF) and proliferation-inducing ligand (APRIL) (see, e.g., Mackay et al., 2003 and Kalled et al., Immunological Reviews, 204: 43-54, 2005). Among non-malignant cells, BCMA has been reported to be expressed primarily on plasma cells and a subset of mature B cells (see, e.g., Laabi et al., EMBO J., 77(1): 3897-3904, 1992; Laabi et al., Nucleic Acids Res., 22(7): 1147-1154, 1994; Kalled et al., 2005; O'Connor et al., J. Exp. Medicine, 199(1): 91-97, 2004; and Ng et al., J. Immunol., 73(2): 807-817, 2004. Mice deficient in BCMA are healthy and have normal numbers of B cells, but have impaired survival of long-lived plasma cells (see, e.g., O'Connor et al., 2004; Xu et al., Mol. Cell. Biol., 21(12): 4067-4074, 2001; and Schiemann et al., Science, 293(5537): 2 111-21 14, 2001).BCMA RNA has been ubiquitously detected in multiple myeloma cells and other lymphomas, and BCMA protein has been detected by some investigators on the surface of plasma cells from multiple myeloma patients (see, e.g., Novak et al., Blood, 103(2): 689-694, 2004; Neri et al., Clinical Cancer Research, 73(19): 5903-5909, 2007; Bellucci et al., Blood, 105(10): 3945-3950, 2005; and Moreaux et al., Blood, 703(8): 3148-3157, 2004).

[0229] In one aspect, provided herein is a method for treating, for example, a tumor or cancer in a subject in need thereof, comprising: (a) administering stem cell transplantation (SCT) to the subject; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 6 months after step (a); (c) producing T cells from the PBMCs; and then (d) administering the produced T cells to the subject. In a specific embodiment, step (b) is performed at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a). In a specific embodiment, step (b) is performed at least about 9 months after step (a). In a specific embodiment, step (b) is performed at least about 12 months after step (a).

[0230] In another aspect, provided herein is a method for treating a tumor or cancer in a subject in need thereof, the method comprising: (a) administering a stem cell transplant (SCT) to the subject; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 9 months after step (a); (c) producing T cells from the PBMCs; and then (d) administering the produced T cells to the subject. In a specific embodiment, step (b) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a). In a specific embodiment, step (b) is performed at least about 12 months after step (a).

[0231] In certain embodiments of the methods provided herein, the methods include determining T cell functionality, e.g., T cell senescence (e.g., prior to leukapheresis), e.g., by determining the proportion of senescent T cells, the proportion of naive T cells, and / or the proportion of CD4:CD8 T cells. In the methods provided herein, the determining can be performed using standard techniques well known to those of skill in the relevant art. For example, in the methods provided herein, the determining can be performed by utilizing techniques such as immunophenotyping of PBMCs, or, in the case of markers associated with T cell differentiation, memory, senescence, and / or exhaustion, by multicolor flow cytometry.

[0232] In specific embodiments, step (b) is performed at least about 6 months to about 18 months after step (a), at least about 6 months to about 17 months after step (a), at least about 6 months to about 16 months after step (a), at least about 6 months to about 15 months after step (a), at least about 6 months to about 14 months after step (a), at least about 6 months to about 13 months after step (a), at least about 6 months to about 12 months after step (a), at least about 6 months to about 11 months after step (a), at least about 6 months to about 10 months after step (a), at least about 6 months to about 9 months after step (a), at least about 6 months to about 8 months after step (a), or at least about 6 months to about 7 months after step (a). In specific embodiments, step (b) is performed at least about 7 months to about 18 months after step (a), at least about 7 months to about 17 months after step (a), at least about 7 months to about 16 months after step (a), at least about 7 months to about 15 months after step (a), at least about 7 months to about 14 months after step (a), at least about 7 months to about 13 months after step (a), at least about 7 months to about 12 months after step (a), at least about 7 months to about 11 months after step (a), at least about 7 months to about 10 months after step (a), at least about 7 months to about 9 months after step (a), or at least about 7 months to about 8 months after step (a). In specific embodiments, step (b) is performed at least about 8 months to about 18 months after step (a), at least about 8 months to about 17 months after step (a), at least about 8 months to about 16 months after step (a), at least about 8 months to about 15 months after step (a), at least about 8 months to about 14 months after step (a), at least about 8 months to about 13 months after step (a), at least about 8 months to about 12 months after step (a), at least about 8 months to about 11 months after step (a), at least about 8 months to about 10 months after step (a), or at least about 8 months to about 9 months after step (a).In specific embodiments, step (b) is performed at least about 9 months to about 18 months after step (a), at least about 9 months to about 17 months after step (a), at least about 9 months to about 16 months after step (a), at least about 9 months to about 15 months after step (a), at least about 9 months to about 14 months after step (a), at least about 9 months to about 13 months after step (a), at least about 9 months to about 12 months after step (a), at least about 9 months to about 11 months after step (a), or at least about 9 months to about 10 months after step (a). In specific embodiments, step (b) is performed at least about 9 months to about 15 months after step (a). In specific embodiments, step (b) is performed at least about 9 months to about 12 months after step (a). In specific embodiments, step (b) is performed at least about 10 months to about 18 months after step (a), at least about 10 months to about 17 months after step (a), at least about 10 months to about 16 months after step (a), at least about 10 months to about 15 months after step (a), at least about 10 months to about 14 months after step (a), at least about 10 months to about 13 months after step (a), at least about 10 months to about 12 months after step (a), or at least about 10 months to about 11 months after step (a). In specific embodiments, step (b) is performed at least about 11 to about 18 months after step (a), at least about 11 to about 17 months after step (a), at least about 11 to about 16 months after step (a), at least about 11 to about 15 months after step (a), at least about 11 to about 14 months after step (a), at least about 11 to about 13 months after step (a), or at least about 11 to about 12 months after step (a). In specific embodiments, step (b) is performed at least about 12 to about 18 months after step (a), at least about 12 to about 17 months after step (a), at least about 12 to about 16 months after step (a), at least about 12 to about 15 months after step (a), at least about 12 to about 14 months after step (a), or at least about 12 to about 13 months after step (a). In a specific embodiment, step (b) occurs at least about 12 months to about 15 months after step (a).In specific embodiments, step (b) is performed at least about 13 to about 18 months after step (a), at least about 13 to about 17 months after step (a), at least about 13 to about 16 months after step (a), at least about 13 to about 15 months after step (a), or at least about 13 to about 14 months after step (a). In specific embodiments, step (b) is performed at least about 14 to about 18 months after step (a), at least about 14 to about 17 months after step (a), at least about 14 to about 16 months after step (a), or at least about 14 to about 15 months after step (a). In specific embodiments, step (b) is performed at least about 15 to about 18 months after step (a), at least about 15 to about 17 months after step (a), or at least about 15 to about 16 months after step (a). In a specific embodiment, step (b) is performed at least about 16 to about 18 months after step (a), or at least about 16 to about 17 months after step (a). In a specific embodiment, step (b) is performed at least about 17 to about 18 months after step (a).

[0233] In another specific embodiment, step (b) is performed at least about 8 or 9 months to about 14 months after step (a), at least about 8 or 9 months to about 13 months after step (a), at least about 8 or 9 months to about 12 months after step (a), at least about 8 or 9 months to about 11 months after step (a), or at least about 8 or 9 months to about 10 months after step (a). In another specific embodiment, step (b) is performed at least about 8 or 9 months to about 12 months after step (a).

[0234] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy-type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma.

[0235] In a specific embodiment, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma. In a specific embodiment, the multiple myeloma is high-risk multiple myeloma or is relapsed and / or refractory multiple myeloma. In a specific embodiment, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, which is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0236] In specific embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In specific embodiments, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In specific embodiments, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In specific embodiments, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In specific embodiments, the stem cell transplant is autologous stem cell transplant. In specific embodiments, the stem cell transplant is allogeneic stem cell transplant.

[0237] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0238] In certain embodiments, the subject is a human.

[0239] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0240] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0241] In another aspect, provided herein is a method of treating a tumor or cancer in a subject in need thereof, comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells from the PBMCs; and then (c) administering the produced T cells to the subject, wherein prior to step (a), the subject has previously undergone a stem cell transplant (SCT) as part of treatment for the tumor or cancer.

[0242] In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 9 months prior to step (a). In a specific embodiment, the subject has undergone a prior SCT at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to step (a). In a specific embodiment, the subject has undergone a prior SCT at least about 12 months prior to step (a).

[0243] In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to step (a). In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 9 months prior to step (a). In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 12 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 6 months to about 18 months prior to step (a), at least about 6 months to about 17 months prior to step (a), at least about 6 months to about 16 months prior to step (a), at least about 6 months to about 15 months prior to step (a), at least about 6 months to about 14 months prior to step (a), at least about 6 months to about 13 months prior to step (a), at least about 6 months to about 12 months prior to step (a), at least about 6 months to about 11 months prior to step (a), at least about 6 months to about 10 months prior to step (a), at least about 6 months to about 9 months prior to step (a), at least about 6 months to about 8 months prior to step (a), or at least about 6 months to about 7 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 7 months to about 18 months prior to step (a), at least about 7 months to about 17 months prior to step (a), at least about 7 months to about 16 months prior to step (a), at least about 7 months to about 15 months prior to step (a), at least about 7 months to about 14 months prior to step (a), at least about 7 months to about 13 months prior to step (a), at least about 7 months to about 12 months prior to step (a), at least about 7 months to about 11 months prior to step (a), at least about 7 months to about 10 months prior to step (a), at least about 7 months to about 9 months prior to step (a), or at least about 7 months to about 8 months prior to step (a).In specific embodiments, the subject has undergone a prior stem cell transplant at least about 8 months to about 18 months prior to step (a), at least about 8 months to about 17 months prior to step (a), at least about 8 months to about 16 months prior to step (a), at least about 8 months to about 15 months prior to step (a), at least about 8 months to about 14 months prior to step (a), at least about 8 months to about 13 months prior to step (a), at least about 8 months to about 12 months prior to step (a), at least about 8 months to about 11 months prior to step (a), at least about 8 months to about 10 months prior to step (a), or at least about 8 months to about 9 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 9 months to about 18 months prior to step (a), at least about 9 months to about 17 months prior to step (a), at least about 9 months to about 16 months prior to step (a), at least about 9 months to about 15 months prior to step (a), at least about 9 months to about 14 months prior to step (a), at least about 9 months to about 13 months prior to step (a), at least about 9 months to about 12 months prior to step (a), at least about 9 months to about 11 months prior to step (a), or at least about 9 months to about 10 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 9 months to about 15 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 9 months to about 12 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 10 months to about 18 months prior to step (a), at least about 10 months to about 17 months prior to step (a), at least about 10 months to about 16 months prior to step (a), at least about 10 months to about 15 months prior to step (a), at least about 10 months to about 14 months prior to step (a), at least about 10 months to about 13 months prior to step (a), at least about 10 months to about 12 months prior to step (a), or at least about 10 months to about 11 months prior to step (a).In specific embodiments, the subject has undergone a prior stem cell transplant at least about 11 months to about 18 months prior to step (a), at least about 11 months to about 17 months prior to step (a), at least about 11 months to about 16 months prior to step (a), at least about 11 months to about 15 months prior to step (a), at least about 11 months to about 14 months prior to step (a), at least about 11 months to about 13 months prior to step (a), or at least about 11 months to about 12 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 12 months to about 18 months prior to step (a), at least about 12 months to about 17 months prior to step (a), at least about 12 months to about 16 months prior to step (a), at least about 12 months to about 15 months prior to step (a), at least about 12 months to about 14 months prior to step (a), or at least about 12 months to about 13 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 12 months to about 15 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 13 months to about 18 months prior to step (a), at least about 13 months to about 17 months prior to step (a), at least about 13 months to about 16 months prior to step (a), at least about 13 months to about 15 months prior to step (a), or at least about 13 months to about 14 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 14 months to about 18 months prior to step (a), at least about 14 months to about 17 months prior to step (a), at least about 14 months to about 16 months prior to step (a), or at least about 14 months to about 15 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 15 months to about 18 months prior to step (a), at least about 15 months to about 17 months prior to step (a), or at least about 15 months to about 16 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 16 months to about 18 months prior to step (a), or at least about 16 months to about 17 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 17 months to about 18 months prior to step (a).In another specific embodiment, the subject has undergone a prior stem cell transplant at least about 8 or 9 months to about 14 months prior to step (a), at least about 8 or 9 months to about 13 months prior to step (a), at least about 8 or 9 months to about 12 months prior to step (a), at least about 8 or 9 months to about 11 months prior to step (a), at least about 8 or 9 months to about 10 months prior to step (a), at least about 9 months to about 15 or 16 months prior to step (a), at least about 10 months to at least about 15 or 16 months prior to step (a), at least about 11 months to at least about 15 or 16 months prior to step (a), at least about 12 months to at least about 15 or 16 months prior to step (a), or at least about 13 months to at least about 15 or 16 months prior to step (a). In another specific embodiment, the subject has undergone a prior stem cell transplant at least about 8 or 9 months to at least about 12 months prior to step (a). In another specific embodiment, the subject has undergone a prior stem cell transplant at least about 9 months to at least about 15 or 16 months prior to step (a). In another specific embodiment, the subject has undergone a prior stem cell transplant at least about 12 months to at least about 15 or 16 months prior to step (a).

[0244] In certain embodiments of the methods provided herein, the methods include determining T cell functionality, e.g., T cell senescence (e.g., prior to leukapheresis), e.g., by determining the proportion of senescent T cells, the proportion of naive T cells, and / or the proportion of CD4:CD8 T cells. In the methods provided herein, the determining can be performed using standard techniques well known to those of skill in the relevant art. For example, in the methods provided herein, the determining can be performed by utilizing techniques such as immunophenotyping of PBMCs, or, in the case of markers associated with T cell differentiation, memory, senescence, and / or exhaustion, by multicolor flow cytometry.

[0245] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0246] In specific embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In specific embodiments, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In specific embodiments, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In specific embodiments, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In specific embodiments, the stem cell transplant is autologous stem cell transplant. In specific embodiments, the stem cell transplant is allogeneic stem cell transplant.

[0247] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0248] In certain embodiments, the subject is a human.

[0249] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0250] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0251] In another aspect, provided herein is a method for treating tumor or cancer in a subject in need thereof, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells (e.g., CAR T cells) from the PBMCs; and then (c) administering the produced T cells (e.g., CAR T cells) to the subject, wherein the subject has previously undergone stem cell transplantation as part of cancer treatment; and step (a) is performed at least about 6 months after the subject has undergone stem cell transplantation. In certain embodiments, step (a) is performed at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has undergone stem cell transplantation. In certain embodiments, step (a) is performed at least about 9 months after the subject has undergone stem cell transplantation. In certain embodiments, step (a) is performed at least about 12 months after the subject has undergone a stem cell transplant.

[0252] In another aspect, provided herein is a method of treating a tumor or cancer in a subject in need thereof, comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells (e.g., CAR T cells) from the PBMCs; and then (c) administering the produced T cells (e.g., CAR T cells) to the subject, wherein the subject has previously undergone a stem cell transplant (SCT) as part of treatment for the tumor or cancer; and step (a) is performed at least about 9 months after the subject has undergone the stem cell transplant.

[0253] In specific embodiments, step (a) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has undergone SCT. In specific embodiments, step (a) is performed at least about 12 months after the subject has undergone SCT.

[0254] In specific embodiments, step (a) is performed at least about 6 months to about 18 months after the subject has undergone stem cell transplantation, at least about 6 months to about 17 months after the subject has undergone stem cell transplantation, at least about 6 months to about 16 months after the subject has undergone stem cell transplantation, at least about 6 months to about 15 months after the subject has undergone stem cell transplantation, at least about 6 months to about 14 months after the subject has undergone stem cell transplantation, at least about 6 months to about 13 months after the subject has undergone stem cell transplantation, at least about 6 months to about 12 months after the subject has undergone stem cell transplantation, at least about 6 months to about 11 months after the subject has undergone stem cell transplantation, at least about 6 months to about 10 months after the subject has undergone stem cell transplantation, at least about 6 months to about 9 months after the subject has undergone stem cell transplantation, at least about 6 months to about 8 months after the subject has undergone stem cell transplantation, or at least about 6 months to about 7 months after the subject has undergone stem cell transplantation. In specific embodiments, step (a) is performed at least about 7 months to about 18 months after the subject receives a stem cell transplant, at least about 7 months to about 17 months after the subject receives a stem cell transplant, at least about 7 months to about 16 months after the subject receives a stem cell transplant, at least about 7 months to about 15 months after the subject receives a stem cell transplant, at least about 7 months to about 14 months after the subject receives a stem cell transplant, at least about 7 months to about 13 months after the subject receives a stem cell transplant, at least about 7 months to about 12 months after the subject receives a stem cell transplant, at least about 7 months to about 11 months after the subject receives a stem cell transplant, at least about 7 months to about 10 months after the subject receives a stem cell transplant, at least about 7 months to about 9 months after the subject receives a stem cell transplant, or at least about 7 months to about 8 months after the subject receives a stem cell transplant.In specific embodiments, step (a) is performed at least about 8 months to about 18 months after the subject receives a stem cell transplant, at least about 8 months to about 17 months after the subject receives a stem cell transplant, at least about 8 months to about 16 months after the subject receives a stem cell transplant, at least about 8 months to about 15 months after the subject receives a stem cell transplant, at least about 8 months to about 14 months after the subject receives a stem cell transplant, at least about 8 months to about 13 months after the subject receives a stem cell transplant, at least about 8 months to about 12 months after the subject receives a stem cell transplant, at least about 8 months to about 11 months after the subject receives a stem cell transplant, at least about 8 months to about 10 months after the subject receives a stem cell transplant, or at least about 8 months to about 9 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 9 months to about 18 months after the subject receives a stem cell transplant, at least about 9 months to about 17 months after the subject receives a stem cell transplant, at least about 9 months to about 16 months after the subject receives a stem cell transplant, at least about 9 months to about 15 months after the subject receives a stem cell transplant, at least about 9 months to about 14 months after the subject receives a stem cell transplant, at least about 9 months to about 13 months after the subject receives a stem cell transplant, at least about 9 months to about 12 months after the subject receives a stem cell transplant, at least about 9 months to about 11 months after the subject receives a stem cell transplant, or at least about 9 months to about 10 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 9 months to about 15 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 9 months to about 12 months after the subject receives a stem cell transplant.In specific embodiments, step (a) is performed at least about 10 months to about 18 months after the subject receives a stem cell transplant, at least about 10 months to about 17 months after the subject receives a stem cell transplant, at least about 10 months to about 16 months after the subject receives a stem cell transplant, at least about 10 months to about 15 months after the subject receives a stem cell transplant, at least about 10 months to about 14 months after the subject receives a stem cell transplant, at least about 10 months to about 13 months after the subject receives a stem cell transplant, at least about 10 months to about 12 months after the subject receives a stem cell transplant, or at least about 10 months to about 11 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 11 months to about 18 months after the subject receives a stem cell transplant, at least about 11 months to about 17 months after the subject receives a stem cell transplant, at least about 11 months to about 16 months after the subject receives a stem cell transplant, at least about 11 months to about 15 months after the subject receives a stem cell transplant, at least about 11 months to about 14 months after the subject receives a stem cell transplant, at least about 11 months to about 13 months after the subject receives a stem cell transplant, or at least about 11 months to about 12 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 12 months to about 18 months after the subject receives a stem cell transplant, at least about 12 months to about 17 months after the subject receives a stem cell transplant, at least about 12 months to about 16 months after the subject receives a stem cell transplant, at least about 12 months to about 15 months after the subject receives a stem cell transplant, at least about 12 months to about 14 months after the subject receives a stem cell transplant, or at least about 12 months to about 13 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 12 months to about 15 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 13 months to about 18 months after the subject receives a stem cell transplant, at least about 13 months to about 17 months after the subject receives a stem cell transplant, at least about 13 months to about 16 months after the subject receives a stem cell transplant, at least about 13 months to about 15 months after the subject receives a stem cell transplant, or at least about 13 months to about 14 months after step (a).In specific embodiments, step (a) is performed at least about 14 months to about 18 months after the subject receives a stem cell transplant, at least about 14 months to about 17 months after the subject receives a stem cell transplant, at least about 14 months to about 16 months after the subject receives a stem cell transplant, or at least about 14 months to about 15 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 15 months to about 18 months after the subject receives a stem cell transplant, at least about 15 months to about 17 months after the subject receives a stem cell transplant, or at least about 15 months to about 16 months after step (a). In specific embodiments, step (a) is performed at least about 16 months to about 18 months after the subject receives a stem cell transplant, or at least about 16 months to about 17 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 17 months to about 18 months after the subject receives a stem cell transplant.

[0255] In another specific embodiment, step (a) is performed at least about 8 or 9 months to about 14 months after the subject has undergone stem cell transplantation, at least about 8 or 9 months to about 13 months after the subject has undergone stem cell transplantation, at least about 8 or 9 months to about 12 months after the subject has undergone stem cell transplantation, at least about 8 or 9 months to about 11 months after the subject has undergone stem cell transplantation, at least about 8 or 9 months to about 10 months after the subject has undergone stem cell transplantation, at least about 9 months to about 15 or 16 months after the subject has undergone stem cell transplantation, at least about 10 months to at least about 15 or 16 months after the subject has undergone stem cell transplantation, at least about 11 months to at least about 15 or 16 months after the subject has undergone stem cell transplantation, at least about 12 months to at least about 15 or 16 months after the subject has undergone stem cell transplantation, or 13 months to about 15 or 16 months after the subject has undergone stem cell transplantation. In another specific embodiment, step (a) is performed at least about 8 or 9 months to about 12 months after the subject receives the stem cell transplant. In another specific embodiment, step (a) is performed at least about 9 months to at least about 15 or 16 months after the subject receives the stem cell transplant. In another specific embodiment, step (a) is performed at least about 12 months to at least about 15 or 16 months after the subject receives the stem cell transplant.

[0256] In certain embodiments of the methods provided herein, the methods include determining T cell functionality, e.g., T cell senescence (e.g., prior to leukapheresis), e.g., by determining the proportion of senescent T cells, the proportion of naive T cells, and / or the proportion of CD4:CD8 T cells. In the methods provided herein, the determining can be performed using standard techniques well known to those of skill in the relevant art. For example, in the methods provided herein, the determining can be performed by utilizing techniques such as immunophenotyping of PBMCs, or, in the case of markers associated with T cell differentiation, memory, senescence, and / or exhaustion, by multicolor flow cytometry.

[0257] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0258] In specific embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In specific embodiments, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In specific embodiments, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In specific embodiments, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In specific embodiments, the stem cell transplant is autologous stem cell transplant. In specific embodiments, the stem cell transplant is allogeneic stem cell transplant.

[0259] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0260] In certain embodiments, the subject is a human.

[0261] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0262] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0263] In another aspect, provided herein is a method of treating a tumor or cancer in a subject in need thereof, wherein the subject has been administered a stem cell transplant, the method comprising: (a) determining that the subject has not been administered a stem cell transplant in less than about six months prior to the determining step; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (c) producing T cells from the PBMCs; and then (d) administering the produced T cells to the subject.

[0264] In another aspect, provided herein is a method for treating a tumor or cancer in a subject in need thereof, wherein the subject has received a stem cell transplant, the method comprising: (a) determining that the subject has not received a stem cell transplant (SCT) for less than about 9 months prior to the determining step; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (c) producing T cells from the PBMCs; and then (d) administering the produced T cells to the subject. In certain embodiments, in step (a), the subject has not received a stem cell transplant (SCT) for less than about 10 months, less than about 11 months, less than about 12 months, less than about 13 months, less than about 14 months, less than about 15 months, less than about 16 months, less than about 17 months, or less than about 18 months prior to the determining step. In certain embodiments, in step (a), the subject has not received a stem cell transplant (SCT) for less than about 12 months prior to the determining step.

[0265] In certain embodiments, in step (a), the subject has not been administered a stem cell transplant for less than about 6 months, less than about 7 months, less than about 8 months, less than about 9 months, less than about 10 months, less than about 11 months, less than about 12 months, less than about 13 months, less than about 14 months, less than about 15 months, less than about 16 months, less than about 17 months, or less than about 18 months prior to the determining step. In certain embodiments, in step (a), the subject has not been administered a stem cell transplant for less than about 9 months prior to the determining step. In certain embodiments, in step (a), the subject has not been administered a stem cell transplant for less than about 12 months prior to the determining step.

[0266] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0267] In specific embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In specific embodiments, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In specific embodiments, the stem cell transplant is autologous stem cell transplant. In specific embodiments, the stem cell transplant is allogeneic stem cell transplant.

[0268] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0269] In certain embodiments, the subject is a human.

[0270] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0271] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0272] In another aspect, provided herein is a method for treating tumor or cancer in a subject in need thereof, wherein the subject has undergone stem cell transplantation (SCT), the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells from the PBMCs; and then (c) administering the produced T cells to the subject, wherein at the time of isolation, the subject has been determined to have undergone stem cell transplantation (SCT) at least about 6 months ago. In certain embodiments, the subject has been determined to have undergone stem cell transplantation at least about 6 months ago, at least about 7 months ago, at least about 8 months ago, at least about 9 months ago, at least about 10 months ago, at least about 11 months ago, at least about 12 months ago, at least about 13 months ago, at least about 14 months ago, at least about 15 months ago, at least about 16 months ago, at least about 17 months ago, or at least about 18 months ago. In certain embodiments, the subject has been determined to have undergone stem cell transplantation at least about 9 months ago. In certain embodiments, the subject has been determined to have received a stem cell transplant at least about 12 months prior.

[0273] In another aspect, provided herein is a method for treating tumor or cancer in a subject in need thereof, wherein the subject has undergone stem cell transplantation (SCT), the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing T cells from the PBMCs; and then (c) administering the produced T cells to the subject, wherein at the time of isolation, the subject has been determined to have undergone stem cell transplantation (SCT) at least about 9 months ago. In certain embodiments, the subject has been determined to have undergone SCT at least about 10 months ago, at least about 11 months ago, at least about 12 months ago, at least about 13 months ago, at least about 14 months ago, at least about 15 months ago, at least about 16 months ago, at least about 17 months ago, or at least about 18 months ago. In certain embodiments, the subject has been determined to have undergone SCT at least about 12 months ago.

[0274] In specific embodiments, the subject is determined to have received a stem cell transplant at least about 6 months to about 18 months prior, at least about 6 months to about 17 months prior, at least about 6 months to about 16 months prior, at least about 6 months to about 15 months prior, at least about 6 months to about 14 months prior, at least about 6 months to about 13 months prior, at least about 6 months to about 12 months prior, at least about 6 months to about 11 months prior, at least about 6 months to about 10 months prior, at least about 6 months to about 9 months prior, at least about 6 months to about 8 months prior, or at least about 6 months to about 7 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 7 months to about 18 months prior, at least about 7 months to about 17 months prior, at least about 7 months to about 16 months prior, at least about 7 months to about 15 months prior, at least about 7 months to about 14 months prior, at least about 7 months to about 13 months prior, at least about 7 months to about 12 months prior, at least about 7 months to about 11 months prior, at least about 7 months to about 10 months prior, at least about 7 months to about 9 months prior, or at least about 7 months to about 8 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 8 months to about 18 months, at least about 8 months to about 17 months, at least about 8 months to about 16 months, at least about 8 months to about 15 months, at least about 8 months to about 14 months, at least about 8 months to about 13 months, at least about 8 months to about 12 months, at least about 8 months to about 11 months, at least about 8 months to about 10 months, or at least about 8 months to about 9 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 9 months to about 18 months, at least about 9 months to about 17 months, at least about 9 months to about 16 months, at least about 9 months to about 15 months, at least about 9 months to about 14 months, at least about 9 months to about 13 months, at least about 9 months to about 12 months, at least about 9 months to about 11 months, or at least about 9 months to about 10 months prior. In a specific embodiment, the subject has been determined to have received a stem cell transplant at least about 9 months to about 15 months previously, hi a specific embodiment, the subject has been determined to have received a stem cell transplant at least about 9 months to about 12 months previously.In specific embodiments, the subject is determined to have received a stem cell transplant at least about 10 to about 18 months, at least about 10 to about 17 months, at least about 10 to about 16 months, at least about 10 to about 15 months, at least about 10 to about 14 months, at least about 10 to about 13 months, at least about 10 to about 12 months, or at least about 10 to about 11 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 11 to about 18 months, at least about 11 to about 17 months, at least about 11 to about 16 months, at least about 11 to about 15 months, at least about 11 to about 14 months, at least about 11 to about 13 months, or at least about 11 to about 12 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 12 months to about 18 months, at least about 12 months to about 17 months, at least about 12 months to about 16 months, at least about 12 months to about 15 months, at least about 12 months to about 14 months, or at least about 12 months to about 13 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 12 months to about 15 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 13 months to about 18 months, at least about 13 months to about 17 months, at least about 13 months to about 16 months, at least about 13 months to about 15 months, or at least about 13 months to about 14 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 14 to about 18 months prior, at least about 14 to about 17 months prior, at least about 14 to about 16 months prior, or at least about 14 to about 15 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 15 to about 18 months prior, at least about 15 to about 17 months prior, or at least about 15 to about 16 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 16 to about 18 months prior, or at least about 16 to about 17 months prior.In a specific embodiment, the subject is determined to have received a stem cell transplant at least about 17 months to about 18 months previously.

[0275] In another specific embodiment, the subject is determined to have been administered a stem cell transplant at least about 8 or 9 months to about 14 months, at least about 8 or 9 months to about 13 months, at least about 8 or 9 months to about 12 months, at least about 8 or 9 months to about 11 months, at least about 8 or 9 months to about 10 months, at least about 9 months to about 15 or 16 months, at least about 10 months to at least about 15 or 16 months, at least about 11 months to at least about 15 or 16 months, at least about 12 months to at least about 15 or 16 months, or 13 months to about 15 or 16 months. In another specific embodiment, the subject is determined to have been administered a stem cell transplant at least about 8 or 9 months to about 12 months. In another specific embodiment, the subject is determined to have been administered a stem cell transplant at least about 9 months to at least about 15 or 16 months. In another specific embodiment, the subject has been determined to have received a stem cell transplant at least about 12 months to at least about 15 or 16 months previously.

[0276] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0277] In specific embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In specific embodiments, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In specific embodiments, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In specific embodiments, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In specific embodiments, the stem cell transplant is autologous stem cell transplant. In specific embodiments, the stem cell transplant is allogeneic stem cell transplant.

[0278] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0279] In certain embodiments, the subject is a human.

[0280] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0281] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0282] In another aspect, provided herein is a method for treating tumor or cancer in a subject in need thereof, wherein the subject has received a stem cell transplant, the method comprising administering to the subject T cells expressing chimeric antigen receptors (CAR T cells) prepared from peripheral blood mononuclear cells (PBMCs) isolated from the patient, wherein, at the time the PBMCs are isolated, the subject last received a stem cell transplant at least about 6 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last received a stem cell transplant at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last received a stem cell transplant at least about 9 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent a stem cell transplant at least about 12 months prior to the time the PBMCs are isolated.

[0283] In another aspect, provided herein is a method for treating tumor or cancer in a subject in need thereof, wherein the subject has received stem cell transplantation, the method comprising administering to the subject T cells expressing chimeric antigen receptors (CAR T cells) prepared from peripheral blood mononuclear cells (PBMCs) isolated from the patient, wherein at the time the PBMCs are isolated, the subject last underwent a stem cell transplant at least about 9 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent a stem cell transplant (SCT) at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent a stem cell transplant (SCT) at least about 12 months prior to the time the PBMCs are isolated.

[0284] In specific embodiments, the subject is determined to have received a stem cell transplant at least about 6 months to about 18 months prior to the time the PBMCs are isolated, at least about 6 months to about 17 months prior to the time the PBMCs are isolated, at least about 6 months to about 16 months prior to the time the PBMCs are isolated, at least about 6 months to about 15 months prior to the time the PBMCs are isolated, at least about 6 months to about 14 months prior to the time the PBMCs are isolated, at least about 6 months to about 13 months prior to the time the PBMCs are isolated, at least about 6 months to about 12 months prior to the time the PBMCs are isolated, at least about 6 months to about 11 months prior to the time the PBMCs are isolated, at least about 6 months to about 10 months prior to the time the PBMCs are isolated, at least about 6 months to about 9 months prior to the time the PBMCs are isolated, at least about 6 months to about 8 months prior to the time the PBMCs are isolated, or at least about 6 months to about 7 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 7 months to about 18 months prior to the time the PBMCs are isolated, at least about 7 months to about 17 months prior to the time the PBMCs are isolated, at least about 7 months to about 16 months prior to the time the PBMCs are isolated, at least about 7 months to about 15 months prior to the time the PBMCs are isolated, at least about 7 months to about 14 months prior to the time the PBMCs are isolated, at least about 7 months to about 13 months prior to the time the PBMCs are isolated, at least about 7 months to about 12 months prior to the time the PBMCs are isolated, at least about 7 months to about 11 months prior to the time the PBMCs are isolated, at least about 7 months to about 10 months prior to the time the PBMCs are isolated, at least about 7 months to about 9 months prior to the time the PBMCs are isolated, or at least about 7 months to about 8 months prior to the time the PBMCs are isolated.In specific embodiments, the subject is determined to have received a stem cell transplant at least about 8 months to about 18 months prior to the time the PBMCs are isolated, at least about 8 months to about 17 months prior to the time the PBMCs are isolated, at least about 8 months to about 16 months prior to the time the PBMCs are isolated, at least about 8 months to about 15 months prior to the time the PBMCs are isolated, at least about 8 months to about 14 months prior to the time the PBMCs are isolated, at least about 8 months to about 13 months prior to the time the PBMCs are isolated, at least about 8 months to about 12 months prior to the time the PBMCs are isolated, at least about 8 months to about 11 months prior to the time the PBMCs are isolated, at least about 8 months to about 10 months prior to the time the PBMCs are isolated, or at least about 8 months to about 9 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 9 months to about 18 months prior to the time the PBMCs are isolated, at least about 9 months to about 17 months prior to the time the PBMCs are isolated, at least about 9 months to about 16 months prior to the time the PBMCs are isolated, at least about 9 months to about 15 months prior to the time the PBMCs are isolated, at least about 9 months to about 14 months prior to the time the PBMCs are isolated, at least about 9 months to about 13 months prior to the time the PBMCs are isolated, at least about 9 months to about 12 months prior to the time the PBMCs are isolated, at least about 9 months to about 11 months prior to the time the PBMCs are isolated, or at least about 9 months to about 10 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 9 months to about 15 months prior to the time the PBMCs are isolated. In a specific embodiment, the subject has been determined to have received a stem cell transplant at least about 9 months to about 12 months prior to the time the PBMCs are isolated.In specific embodiments, the subject is determined to have received a stem cell transplant at least about 10 months to about 18 months prior to the time the PBMCs are isolated, at least about 10 months to about 17 months prior to the time the PBMCs are isolated, at least about 10 months to about 16 months prior to the time the PBMCs are isolated, at least about 10 months to about 15 months prior to the time the PBMCs are isolated, at least about 10 months to about 14 months prior to the time the PBMCs are isolated, at least about 10 months to about 13 months prior to the time the PBMCs are isolated, at least about 10 months to about 12 months prior to the time the PBMCs are isolated, or at least about 10 months to about 11 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 11 months to about 18 months prior to the time the PBMCs are isolated, at least about 11 months to about 17 months prior to the time the PBMCs are isolated, at least about 11 months to about 16 months prior to the time the PBMCs are isolated, at least about 11 months to about 15 months prior to the time the PBMCs are isolated, at least about 11 months to about 14 months prior to the time the PBMCs are isolated, at least about 11 months to about 13 months prior to the time the PBMCs are isolated, or at least about 11 months to about 12 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 12 months to about 18 months prior to the time the PBMCs are isolated, at least about 12 months to about 17 months prior to the time the PBMCs are isolated, at least about 12 months to about 16 months prior to the time the PBMCs are isolated, at least about 12 months to about 15 months prior to the time the PBMCs are isolated, at least about 12 months to about 14 months prior to the time the PBMCs are isolated, or at least about 12 months to about 13 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 12 months to about 15 months prior to the time the PBMCs are isolated.In specific embodiments, the subject is determined to have received a stem cell transplant at least about 13 to about 18 months prior to the time the PBMCs are isolated, at least about 13 to about 17 months prior to the time the PBMCs are isolated, at least about 13 to about 16 months prior to the time the PBMCs are isolated, at least about 13 to about 15 months prior to the time the PBMCs are isolated, or at least about 13 to about 14 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 14 to about 18 months prior to the time the PBMCs are isolated, at least about 14 to about 17 months prior to the time the PBMCs are isolated, at least about 14 to about 16 months prior to the time the PBMCs are isolated, or at least about 14 to about 15 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 15 to about 18 months prior to the time the PBMCs are isolated, at least about 15 to about 17 months prior to the time the PBMCs are isolated, or at least about 15 to about 16 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 16 to about 18 months prior to the time the PBMCs are isolated, or at least about 16 to about 17 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 17 to about 18 months prior to the time the PBMCs are isolated.

[0285] In another specific embodiment, the subject last underwent a stem cell transplant at least about 8 or 9 months to about 14 months before the time the PBMCs are isolated, at least about 8 or 9 months to about 13 months before the time the PBMCs are isolated, at least about 8 or 9 months to about 12 months before the time the PBMCs are isolated, at least about 8 or 9 months to about 11 months before the time the PBMCs are isolated, at least about 8 or 9 months to about 10 months before the PBMCs are isolated, at least about 9 months to about 15 or 16 months before the time the PBMCs are isolated, at least about 10 months to at least about 15 or 16 months before the PBMCs are isolated, at least about 11 months to at least about 15 or 16 months before the PBMCs are isolated, at least about 12 months to at least about 15 or 16 months before the PBMCs are isolated, or at least about 13 months to at least about 15 or 16 months before the PBMCs are isolated. In another specific embodiment, the subject received their last stem cell transplant at least about 8 or 9 months to about 12 months before the time the PBMCs are isolated. In another specific embodiment, the subject received their last stem cell transplant at least about 9 months to at least about 15 or 16 months before the time the PBMCs are isolated. In another specific embodiment, the subject received their last stem cell transplant at least about 12 months to at least about 15 or 16 months before the time the PBMCs are isolated.

[0286] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0287] In specific embodiments, the stem cell transplant (SCT) is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In specific embodiments, the stem cell transplant (SCT) is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In specific embodiments, the stem cell transplant (SCT) is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In specific embodiments, the stem cell transplant (SCT) is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In specific embodiments, the stem cell transplant (SCT) is autologous stem cell transplant. In specific embodiments, the stem cell transplant is allogeneic stem cell transplant.

[0288] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0289] In certain embodiments, the subject is a human.

[0290] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0291] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0292] In another aspect, provided herein is a method of treating a tumor or cancer in a subject in need thereof, wherein the subject has received a stem cell transplant, the method comprising administering to the subject T cells expressing chimeric antigen receptors (CAR T cells) that have been prepared from peripheral blood mononuclear cells (PBMCs) isolated from the patient, wherein at the time the PBMCs are isolated, the PBMCs comprise at least about 20% T cells.

[0293] In specific embodiments, the tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenocortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, ... Myosarcoma, Wilms' tumor, glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell Lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), juvenile chronic myeloid leukemia (JCML), juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, aggressive NK-cell leukemia, adult T The cancer is selected from the group consisting of lymphocytic leukemia / lymphoma, extranodal NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sézary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma. In specific embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In a specific embodiment, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In a specific embodiment, the cancer is multiple myeloma.In specific embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma. In specific embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In specific embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0294] In specific embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In specific embodiments, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In specific embodiments, the stem cell transplant is autologous stem cell transplant.

[0295] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0296] In certain embodiments, the subject is a human.

[0297] In certain embodiments, prior to administering the T cells to a subject, the subject undergoes an apheresis procedure, e.g., a leukapheresis procedure, to collect PBMCs for the manufacture of T cells (e.g., CAR T cells).

[0298] In certain embodiments, the T cells (e.g., CAR T cells) are administered by intravenous infusion.

[0299]

[0010] In another aspect, provided herein are methods of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, the methods comprising: (a) administering a stem cell transplant to the subject; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 6 months after step (a); (c) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (d) administering the CAR T cells to the subject. In certain embodiments, step (b) is performed at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a) of administering the stem cell transplant to the subject. In certain embodiments, step (b) occurs at least about 9 months after step (a) of administering a stem cell transplant to the subject. In certain embodiments, step (b) occurs at least about 12 months after step (a) of administering a stem cell transplant to the subject.

[0300] In another aspect, provided herein is a method for treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, the method comprising: (a) administering stem cell transplantation (SCT) to the subject; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 9 months after step (a); (c) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (d) administering the BCMA CAR T cells to the subject. In certain embodiments, step (b) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a) of administering stem cell transplantation (SCT) to the subject. In certain embodiments, step (b) is performed at least about 12 months after step (a) of administering stem cell transplantation (SCT) to the subject.

[0301] In specific embodiments, step (b) is performed at least about 6 months to about 18 months after step (a), at least about 6 months to about 17 months after step (a), at least about 6 months to about 16 months after step (a), at least about 6 months to about 15 months after step (a), at least about 6 months to about 14 months after step (a), at least about 6 months to about 13 months after step (a), at least about 6 months to about 12 months after step (a), at least about 6 months to about 11 months after step (a), at least about 6 months to about 10 months after step (a), at least about 6 months to about 9 months after step (a), at least about 6 months to about 8 months after step (a), or at least about 6 months to about 7 months after step (a). In specific embodiments, step (b) is performed at least about 7 months to about 18 months after step (a), at least about 7 months to about 17 months after step (a), at least about 7 months to about 16 months after step (a), at least about 7 months to about 15 months after step (a), at least about 7 months to about 14 months after step (a), at least about 7 months to about 13 months after step (a), at least about 7 months to about 12 months after step (a), at least about 7 months to about 11 months after step (a), at least about 7 months to about 10 months after step (a), at least about 7 months to about 9 months after step (a), or at least about 7 months to about 8 months after step (a). In specific embodiments, step (b) is performed at least about 8 months to about 18 months after step (a), at least about 8 months to about 17 months after step (a), at least about 8 months to about 16 months after step (a), at least about 8 months to about 15 months after step (a), at least about 8 months to about 14 months after step (a), at least about 8 months to about 13 months after step (a), at least about 8 months to about 12 months after step (a), at least about 8 months to about 11 months after step (a), at least about 8 months to about 10 months after step (a), or at least about 8 months to about 9 months after step (a).In specific embodiments, step (b) is performed at least about 9 months to about 18 months after step (a), at least about 9 months to about 17 months after step (a), at least about 9 months to about 16 months after step (a), at least about 9 months to about 15 months after step (a), at least about 9 months to about 14 months after step (a), at least about 9 months to about 13 months after step (a), at least about 9 months to about 12 months after step (a), at least about 9 months to about 11 months after step (a), or at least about 9 months to about 10 months after step (a). In specific embodiments, step (b) is performed at least about 9 months to about 15 months after step (a). In specific embodiments, step (b) is performed at least about 9 months to about 12 months after step (a). In specific embodiments, step (b) is performed at least about 10 months to about 18 months after step (a), at least about 10 months to about 17 months after step (a), at least about 10 months to about 16 months after step (a), at least about 10 months to about 15 months after step (a), at least about 10 months to about 14 months after step (a), at least about 10 months to about 13 months after step (a), at least about 10 months to about 12 months after step (a), or at least about 10 months to about 11 months after step (a). In specific embodiments, step (b) is performed at least about 11 to about 18 months after step (a), at least about 11 to about 17 months after step (a), at least about 11 to about 16 months after step (a), at least about 11 to about 15 months after step (a), at least about 11 to about 14 months after step (a), at least about 11 to about 13 months after step (a), or at least about 11 to about 12 months after step (a). In specific embodiments, step (b) is performed at least about 12 to about 18 months after step (a), at least about 12 to about 17 months after step (a), at least about 12 to about 16 months after step (a), at least about 12 to about 15 months after step (a), at least about 12 to about 14 months after step (a), or at least about 12 to about 13 months after step (a). In a specific embodiment, step (b) occurs at least about 12 months to about 15 months after step (a).In specific embodiments, step (b) is performed at least about 13 to about 18 months after step (a), at least about 13 to about 17 months after step (a), at least about 13 to about 16 months after step (a), at least about 13 to about 15 months after step (a), or at least about 13 to about 14 months after step (a). In specific embodiments, step (b) is performed at least about 14 to about 18 months after step (a), at least about 14 to about 17 months after step (a), at least about 14 to about 16 months after step (a), or at least about 14 to about 15 months after step (a). In specific embodiments, step (b) is performed at least about 15 to about 18 months after step (a), at least about 15 to about 17 months after step (a), or at least about 15 to about 16 months after step (a). In a specific embodiment, step (b) is performed at least about 16 to about 18 months after step (a), or at least about 16 to about 17 months after step (a). In a specific embodiment, step (b) is performed at least about 17 to about 18 months after step (a).

[0302] In another specific embodiment, step (b) is performed at least about 8 or 9 months to about 14 months after step (a), at least about 8 or 9 months to about 13 months after step (a), at least about 8 or 9 months to about 12 months after step (a), at least about 8 or 9 months to about 11 months after step (a), at least about 8 or 9 months to about 10 months after step (a), at least about 9 months to about 15 or 16 months after step (a), at least about 10 months to at least about 15 or 16 months after step (a), at least about 11 months to at least about 15 or 16 months after step (a), at least about 12 months to at least about 15 or 16 months after step (a), or at least about 13 months to at least about 15 or 16 months after step (a). In another specific embodiment, step (b) is performed at least about 8 or 9 months to about 12 months after step (a). In another specific embodiment, step (b) occurs at least about 9 months to at least about 15 or 16 months after step (a). In another specific embodiment, step (b) occurs at least about 12 months to at least about 15 or 16 months after step (a).

[0303] In certain embodiments of the methods provided herein, the methods include determining T cell functionality, e.g., T cell senescence (e.g., prior to leukapheresis), e.g., by determining the proportion of senescent T cells, the proportion of naive T cells, and / or the proportion of CD4:CD8 T cells. In the methods provided herein, the determining can be performed using standard techniques well known to those of skill in the relevant art. For example, in the methods provided herein, the determining can be performed by utilizing techniques such as immunophenotyping of PBMCs, or, in the case of markers associated with T cell differentiation, memory, senescence, and / or exhaustion, by multicolor flow cytometry.

[0304] In certain embodiments, the cancer is leukemia. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, and the high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0305] In certain embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In a specific embodiment, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In a specific embodiment, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In a specific embodiment, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In a specific embodiment, the stem cell transplant is autologous stem cell transplant. In a specific embodiment, the stem cell transplant is allogeneic stem cell transplant.

[0306] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0307] In certain embodiments, the subject is a human.

[0308] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02 scFv, e.g., SEQ ID NO: 38.

[0309] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0310] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0311]

[0010] In another aspect, provided herein is a method of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (c) administering the BCMA CAR T cells to the subject, wherein prior to step (a), the subject has previously undergone a stem cell transplant as part of a treatment for the cancer. In certain embodiments, the subject has previously undergone a stem cell transplant at least about 9 months prior to step (a). In certain embodiments, the subject has undergone prior SCT at least about 6 months, at least about 7 months, at least about 8 months, 9 months, 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to step (a). In certain embodiments, the subject has undergone prior SCT at least about 12 months prior to step (a).

[0312] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 6 months to about 18 months prior to step (a), at least about 6 months to about 17 months prior to step (a), at least about 6 months to about 16 months prior to step (a), at least about 6 months to about 15 months prior to step (a), at least about 6 months to about 14 months prior to step (a), at least about 6 months to about 13 months prior to step (a), at least about 6 months to about 12 months prior to step (a), at least about 6 months to about 11 months prior to step (a), at least about 6 months to about 10 months prior to step (a), at least about 6 months to about 9 months prior to step (a), at least about 6 months to about 8 months prior to step (a), or at least about 6 months to about 7 months prior to step (a).

[0313] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 7 months to about 18 months prior to step (a), at least about 7 months to about 17 months prior to step (a), at least about 7 months to about 16 months prior to step (a), at least about 7 months to about 15 months prior to step (a), at least about 7 months to about 14 months prior to step (a), at least about 7 months to about 13 months prior to step (a), at least about 7 months to about 12 months prior to step (a), at least about 7 months to about 11 months prior to step (a), at least about 7 months to about 10 months prior to step (a), at least about 7 months to about 9 months prior to step (a), or at least about 7 months to about 8 months prior to step (a).

[0314] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 8 months to about 18 months prior to step (a), at least about 8 months to about 17 months prior to step (a), at least about 8 months to about 16 months prior to step (a), at least about 8 months to about 15 months prior to step (a), at least about 8 months to about 14 months prior to step (a), at least about 8 months to about 13 months prior to step (a), at least about 8 months to about 12 months prior to step (a), at least about 8 months to about 11 months prior to step (a), at least about 8 months to about 10 months prior to step (a), or at least about 8 months to about 9 months prior to step (a).

[0315] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 9 months to about 18 months prior to step (a), at least about 9 months to about 17 months prior to step (a), at least about 9 months to about 16 months prior to step (a), at least about 9 months to about 15 months prior to step (a), at least about 9 months to about 14 months prior to step (a), at least about 9 months to about 13 months prior to step (a), at least about 9 months to about 12 months prior to step (a), at least about 9 months to about 11 months prior to step (a), or at least about 9 months to about 10 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 9 months to about 15 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 9 months to about 12 months prior to step (a).

[0316] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 10 months to about 18 months prior to step (a), at least about 10 months to about 17 months prior to step (a), at least about 10 months to about 16 months prior to step (a), at least about 10 months to about 15 months prior to step (a), at least about 10 months to about 14 months prior to step (a), at least about 10 months to about 13 months prior to step (a), at least about 10 months to about 12 months prior to step (a), or at least about 10 months to about 11 months prior to step (a).

[0317] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 11 months to about 18 months prior to step (a), at least about 11 months to about 17 months prior to step (a), at least about 11 months to about 16 months prior to step (a), at least about 11 months to about 15 months prior to step (a), at least about 11 months to about 14 months prior to step (a), at least about 11 months to about 13 months prior to step (a), or at least about 11 months to about 12 months prior to step (a).

[0318] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 12 months to about 18 months prior to step (a), at least about 12 months to about 17 months prior to step (a), at least about 12 months to about 16 months prior to step (a), at least about 12 months to about 15 months prior to step (a), at least about 12 months to about 14 months prior to step (a), or at least about 12 months to about 13 months prior to step (a). In specific embodiments, the subject has undergone a prior stem cell transplant at least about 12 months to about 15 months prior to step (a).

[0319] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 13 months to about 18 months prior to step (a), at least about 13 months to about 17 months prior to step (a), at least about 13 months to about 16 months prior to step (a), at least about 13 months to about 15 months prior to step (a), or at least about 13 months to about 14 months prior to step (a).

[0320] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 14 months to about 18 months prior to step (a), at least about 14 months to about 17 months prior to step (a), at least about 14 months to about 16 months prior to step (a), or at least about 14 months to about 15 months prior to step (a).

[0321] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 15 months to about 18 months prior to step (a), at least about 15 months to about 17 months prior to step (a), or at least about 15 months to about 16 months prior to step (a).

[0322] In specific embodiments, the subject has undergone a prior stem cell transplant at least about 16 months to about 18 months prior to step (a), or at least about 16 months to about 17 months prior to step (a).

[0323] In a specific embodiment, the subject has undergone a prior stem cell transplant at least about 17 months to about 18 months prior to step (a).

[0324] In another specific embodiment, the subject has undergone a prior stem cell transplant at least about 8 or 9 months to about 14 months prior to step (a), at least about 8 or 9 months to about 13 months prior to step (a), at least about 8 or 9 months to about 12 months prior to step (a), at least about 8 or 9 months to about 11 months prior to step (a), at least about 8 or 9 months to about 10 months prior to step (a), at least about 9 months to about 15 or 16 months prior to step (a), at least about 10 months to at least about 15 or 16 months prior to step (a), at least about 11 months to at least about 15 or 16 months prior to step (a), at least about 12 months to at least about 15 or 16 months prior to step (a), or at least about 13 months to at least about 15 or 16 months prior to step (a). In another specific embodiment, the subject has undergone a prior stem cell transplant at least about 8 or 9 months to about 12 months prior to step (a). In another specific embodiment, the subject has undergone a prior stem cell transplant at least about 9 months to at least about 15 or 16 months prior to step (a). In another specific embodiment, the subject has undergone a prior stem cell transplant at least about 12 months to at least about 15 or 16 months prior to step (a).

[0325] In certain embodiments of the methods provided herein, the methods include determining T cell functionality, e.g., T cell senescence (e.g., prior to leukapheresis), e.g., by determining the proportion of senescent T cells, the proportion of naive T cells, and / or the proportion of CD4:CD8 T cells. In the methods provided herein, the determining can be performed using standard techniques well known to those of skill in the relevant art. For example, in the methods provided herein, the determining can be performed by utilizing techniques such as immunophenotyping of PBMCs, or, in the case of markers associated with T cell differentiation, memory, senescence, and / or exhaustion, by multicolor flow cytometry.

[0326] In certain embodiments, the cancer is leukemia. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is a non-Hodgkin's lymphoma, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.

[0327] In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0328] In certain embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In a specific embodiment, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In a specific embodiment, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In a specific embodiment, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In a specific embodiment, the stem cell transplant is autologous stem cell transplant. In a specific embodiment, the stem cell transplant is allogeneic stem cell transplant.

[0329] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0330] In certain embodiments, the subject is a human.

[0331] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02 scFv, e.g., SEQ ID NO: 38.

[0332] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0333] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0334]

[0009] In another aspect, provided herein are methods of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, the methods comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and (c) administering the BCMA CAR T cells to the subject, wherein the patient has previously undergone stem cell transplantation (SCT) as part of a cancer treatment, and step (a) is performed at least about 6 months after the subject has undergone the stem cell transplantation (SCT). In certain embodiments, step (a) is performed at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has undergone the stem cell transplantation. In certain embodiments, step (a) is performed at least about 9 months after the subject has received a stem cell transplant. In certain embodiments, step (a) is performed at least about 12 months after the subject has received a stem cell transplant.

[0335] In another embodiment, provided herein is a method for treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and (c) administering the BCMA CAR T cells to the subject, wherein the patient has previously undergone stem cell transplantation (SCT) as part of cancer treatment, and step (a) is performed at least about 9 months after the subject has undergone stem cell transplantation (SCT). In certain embodiments, step (a) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after the subject has undergone SCT. In certain embodiments, step (a) is performed at least about 12 months after the subject has undergone SCT.

[0336] In specific embodiments, step (a) is performed at least about 6 months to about 18 months after the subject has undergone stem cell transplantation, at least about 6 months to about 17 months after the subject has undergone stem cell transplantation, at least about 6 months to about 16 months after the subject has undergone stem cell transplantation, at least about 6 months to about 15 months after the subject has undergone stem cell transplantation, at least about 6 months to about 14 months after the subject has undergone stem cell transplantation, at least about 6 months to about 13 months after the subject has undergone stem cell transplantation, at least about 6 months to about 12 months after the subject has undergone stem cell transplantation, at least about 6 months to about 11 months after the subject has undergone stem cell transplantation, at least about 6 months to about 10 months after the subject has undergone stem cell transplantation, at least about 6 months to about 9 months after the subject has undergone stem cell transplantation, at least about 6 months to about 8 months after the subject has undergone stem cell transplantation, or at least about 6 months to about 7 months after the subject has undergone stem cell transplantation. In specific embodiments, step (a) is performed at least about 7 months to about 18 months after the subject receives a stem cell transplant, at least about 7 months to about 17 months after the subject receives a stem cell transplant, at least about 7 months to about 16 months after the subject receives a stem cell transplant, at least about 7 months to about 15 months after the subject receives a stem cell transplant, at least about 7 months to about 14 months after the subject receives a stem cell transplant, at least about 7 months to about 13 months after the subject receives a stem cell transplant, at least about 7 months to about 12 months after the subject receives a stem cell transplant, at least about 7 months to about 11 months after the subject receives a stem cell transplant, at least about 7 months to about 10 months after the subject receives a stem cell transplant, at least about 7 months to about 9 months after the subject receives a stem cell transplant, or at least about 7 months to about 8 months after the subject receives a stem cell transplant.In specific embodiments, step (a) is performed at least about 8 months to about 18 months after the subject receives a stem cell transplant, at least about 8 months to about 17 months after the subject receives a stem cell transplant, at least about 8 months to about 16 months after the subject receives a stem cell transplant, at least about 8 months to about 15 months after the subject receives a stem cell transplant, at least about 8 months to about 14 months after the subject receives a stem cell transplant, at least about 8 months to about 13 months after the subject receives a stem cell transplant, at least about 8 months to about 12 months after the subject receives a stem cell transplant, at least about 8 months to about 11 months after the subject receives a stem cell transplant, at least about 8 months to about 10 months after the subject receives a stem cell transplant, or at least about 8 months to about 9 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 9 months to about 18 months after the subject receives a stem cell transplant, at least about 9 months to about 17 months after the subject receives a stem cell transplant, at least about 9 months to about 16 months after the subject receives a stem cell transplant, at least about 9 months to about 15 months after the subject receives a stem cell transplant, at least about 9 months to about 14 months after the subject receives a stem cell transplant, at least about 9 months to about 13 months after the subject receives a stem cell transplant, at least about 9 months to about 12 months after the subject receives a stem cell transplant, at least about 9 months to about 11 months after the subject receives a stem cell transplant, or at least about 9 months to about 10 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 9 months to about 15 months after the subject receives a stem cell transplant, or at least about 12 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 9 months to about 12 months after the subject receives a stem cell transplant, or at least about 12 months after the subject receives a stem cell transplant.In specific embodiments, step (a) is performed at least about 10 months to about 18 months after the subject receives a stem cell transplant, at least about 10 months to about 17 months after the subject receives a stem cell transplant, at least about 10 months to about 16 months after the subject receives a stem cell transplant, at least about 10 months to about 15 months after the subject receives a stem cell transplant, at least about 10 months to about 14 months after the subject receives a stem cell transplant, at least about 10 months to about 13 months after the subject receives a stem cell transplant, at least about 10 months to about 12 months after the subject receives a stem cell transplant, or at least about 10 months to about 11 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 11 months to about 18 months after the subject receives a stem cell transplant, at least about 11 months to about 17 months after the subject receives a stem cell transplant, at least about 11 months to about 16 months after the subject receives a stem cell transplant, at least about 11 months to about 15 months after the subject receives a stem cell transplant, at least about 11 months to about 14 months after the subject receives a stem cell transplant, at least about 11 months to about 13 months after the subject receives a stem cell transplant, or at least about 11 months to about 12 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 12 months to about 18 months after the subject receives a stem cell transplant, at least about 12 months to about 17 months after the subject receives a stem cell transplant, at least about 12 months to about 16 months after the subject receives a stem cell transplant, at least about 12 months to about 15 months after the subject receives a stem cell transplant, at least about 12 months to about 14 months after the subject receives a stem cell transplant, or at least about 12 months to about 13 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 12 months to about 15 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 13 months to about 18 months after the subject receives a stem cell transplant, at least about 13 months to about 17 months after the subject receives a stem cell transplant, at least about 13 months to about 16 months after the subject receives a stem cell transplant, at least about 13 months to about 15 months after the subject receives a stem cell transplant, or at least about 13 months to about 14 months after step (a).In specific embodiments, step (a) is performed at least about 14 months to about 18 months after the subject receives a stem cell transplant, at least about 14 months to about 17 months after the subject receives a stem cell transplant, at least about 14 months to about 16 months after the subject receives a stem cell transplant, or at least about 14 months to about 15 months after the subject receives a stem cell transplant.

[0337] In specific embodiments, step (a) is performed at least about 15 months to about 18 months after the subject receives a stem cell transplant, at least about 15 months to about 17 months after the subject receives a stem cell transplant, or at least about 15 months to about 16 months after step (a). In specific embodiments, step (a) is performed at least about 16 months to about 18 months after the subject receives a stem cell transplant, or at least about 16 months to about 17 months after the subject receives a stem cell transplant. In specific embodiments, step (a) is performed at least about 17 months to about 18 months after the subject receives a stem cell transplant.

[0338] In another specific embodiment, step (a) is performed at least about 8 or 9 months to about 14 months after the subject has undergone stem cell transplantation, at least about 8 or 9 months to about 13 months after the subject has undergone stem cell transplantation, at least about 8 or 9 months to about 12 months after the subject has undergone stem cell transplantation, at least about 8 or 9 months to about 11 months after the subject has undergone stem cell transplantation, at least about 8 or 9 months to about 10 months after the subject has undergone stem cell transplantation, at least about 9 months to about 15 or 16 months after the subject has undergone stem cell transplantation, at least about 10 months to at least about 15 or 16 months after the subject has undergone stem cell transplantation, at least about 11 months to at least about 15 or 16 months after the subject has undergone stem cell transplantation, at least about 12 months to at least about 15 or 16 months after the subject has undergone stem cell transplantation, or at least about 13 months to at least about 15 or 16 months after the subject has undergone stem cell transplantation. In another specific embodiment, step (a) is performed at least about 8 or 9 months to about 12 months after the subject receives the stem cell transplant. In another specific embodiment, step (a) is performed at least about 9 months to at least about 15 or 16 months after the subject receives the stem cell transplant. In another specific embodiment, step (a) is performed at least about 12 months to at least about 15 or 16 months after the subject receives the stem cell transplant. In certain embodiments, the cancer is leukemia. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is a non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is a non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma.In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0339] In certain embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In a specific embodiment, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In a specific embodiment, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In a specific embodiment, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In a specific embodiment, the stem cell transplant is an allogeneic stem cell transplant. In a specific embodiment, the stem cell transplant is an autologous stem cell transplant.

[0340] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0341] In certain embodiments, the subject is a human.

[0342] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02 scFv, e.g., SEQ ID NO: 38.

[0343] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0344] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0345] In another aspect, provided herein is a method of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need thereof, wherein the subject has received a stem cell transplant (SCT) as part of treatment for the cancer, the method comprising: (a) determining that the subject has not received a stem cell transplant less than about 6 months prior to the determining step; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject, wherein the isolation occurs at least 6 months after the stem cell transplant has been administered to the subject; (c) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (d) administering the BCMA CAR T cells to the subject. In certain embodiments, in step (a), the subject has not received a stem cell transplant for less than about 6 months, less than about 7 months, less than about 8 months, less than about 9 months, less than about 10 months, less than about 11 months, less than about 12 months, less than about 13 months, less than about 14 months, less than about 15 months, less than about 16 months, less than about 17 months, or less than about 18 months prior to the determining step. In certain embodiments, in step (a), the subject has not received a stem cell transplant for less than about 9 months prior to the determining step. In certain embodiments, in step (a), the subject has not received a stem cell transplant for less than about 12 months prior to the determining step.

[0346] In another aspect, provided herein is a method for treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need of treatment, wherein the subject has received stem cell transplantation (SCT) as part of the cancer treatment, the method comprising: (a) determining that the subject has not received SCT for less than about 9 months prior to the determining step; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject, the step being performed at least 9 months after the SCT has been administered to the subject; (c) producing chimeric antigen receptor (CAR) T cells against BCMA from the PBMCs; and then (d) producing chimeric antigen receptor (CAR) T cells against BCMA. In certain embodiments, in step (a), the subject has not received SCT for less than about 10 months, less than about 11 months, less than about 12 months, less than about 13 months, less than about 14 months, less than about 15 months, less than about 16 months, less than about 17 months, or less than about 18 months prior to the determining step. In certain embodiments, in step (a), the subject has not received an SCT in less than about 12 months prior to the determining step.

[0347] In certain embodiments, the cancer is leukemia. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, and the high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0348] In certain embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In a specific embodiment, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In a specific embodiment, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In a specific embodiment, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In a specific embodiment, the stem cell transplant is autologous stem cell transplant. In a specific embodiment, the stem cell transplant is allogeneic stem cell transplant.

[0349] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0350] In certain embodiments, the subject is a human.

[0351] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02 scFv, e.g., SEQ ID NO: 38.

[0352] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0353] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0354] In another aspect, provided herein is a method of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need thereof, wherein the subject has received a stem cell transplant, the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (c) administering the BCMA CAR T cells to the subject, wherein at the time of isolation, it has been determined that the subject received the stem cell transplant at least about 6 months previously. In certain embodiments, it has been determined that the subject received the stem cell transplant at least about 6 months previously, at least about 7 months previously, at least about 8 months previously, at least about 9 months previously, at least about 10 months previously, at least about 11 months previously, at least about 12 months previously, at least about 13 months previously, at least about 14 months previously, at least about 15 months previously, at least about 16 months previously, at least about 17 months previously, or at least about 18 months previously. In certain embodiments, the subject has been determined to have received a stem cell transplant at least about 9 months prior, hi certain embodiments, the subject has been determined to have received a stem cell transplant at least about 12 months prior.

[0355] In another aspect, provided herein is a method for treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need thereof, wherein the subject has received a stem cell transplant (SCT), the method comprising: (a) isolating peripheral blood mononuclear cells (PBMCs) from the subject; (b) producing chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) from the PBMCs; and then (c) administering the BCMA CAR T cells to the subject, wherein at the time of isolation, the subject has been determined to have received the SCT at least about 9 months prior. In certain embodiments, the subject has been determined to have received the stem cell transplant (SCT) at least about 10 months prior, at least about 11 months prior, at least about 12 months prior, at least about 13 months prior, at least about 14 months prior, at least about 15 months prior, at least about 16 months prior, at least about 17 months prior, or at least about 18 months prior. In certain embodiments, the subject has been determined to have received the stem cell transplant (SCT) at least about 12 months prior.

[0356] In specific embodiments, the subject is determined to have received a stem cell transplant at least about 6 months to about 18 months prior, at least about 6 months to about 17 months prior, at least about 6 months to about 16 months prior, at least about 6 months to about 15 months prior, at least about 6 months to about 14 months prior, at least about 6 months to about 13 months prior, at least about 6 months to about 12 months prior, at least about 6 months to about 11 months prior, at least about 6 months to about 10 months prior, at least about 6 months to about 9 months prior, at least about 6 months to about 8 months prior, or at least about 6 months to about 7 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 7 months to about 18 months prior, at least about 7 months to about 17 months prior, at least about 7 months to about 16 months prior, at least about 7 months to about 15 months prior, at least about 7 months to about 14 months prior, at least about 7 months to about 13 months prior, at least about 7 months to about 12 months prior, at least about 7 months to about 11 months prior, at least about 7 months to about 10 months prior, at least about 7 months to about 9 months prior, or at least about 7 months to about 8 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 8 months to about 18 months, at least about 8 months to about 17 months, at least about 8 months to about 16 months, at least about 8 months to about 15 months, at least about 8 months to about 14 months, at least about 8 months to about 13 months, at least about 8 months to about 12 months, at least about 8 months to about 11 months, at least about 8 months to about 10 months, or at least about 8 months to about 9 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 9 months to about 18 months, at least about 9 months to about 17 months, at least about 9 months to about 16 months, at least about 9 months to about 15 months, at least about 9 months to about 14 months, at least about 9 months to about 13 months, at least about 9 months to about 12 months, at least about 9 months to about 11 months, or at least about 9 months to about 10 months prior. In a specific embodiment, the subject has been determined to have received a stem cell transplant at least about 9 months to about 15 months previously, hi a specific embodiment, the subject has been determined to have received a stem cell transplant at least about 9 months to about 12 months previously.In specific embodiments, the subject is determined to have received a stem cell transplant at least about 10 to about 18 months, at least about 10 to about 17 months, at least about 10 to about 16 months, at least about 10 to about 15 months, at least about 10 to about 14 months, at least about 10 to about 13 months, at least about 10 to about 12 months, or at least about 10 to about 11 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 11 to about 18 months, at least about 11 to about 17 months, at least about 11 to about 16 months, at least about 11 to about 15 months, at least about 11 to about 14 months, at least about 11 to about 13 months, or at least about 11 to about 12 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 12 months to about 18 months, at least about 12 months to about 17 months, at least about 12 months to about 16 months, at least about 12 months to about 15 months, at least about 12 months to about 14 months, or at least about 12 months to about 13 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 12 months to about 15 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 13 months to about 18 months, at least about 13 months to about 17 months, at least about 13 months to about 16 months, at least about 13 months to about 15 months, or at least about 13 months to about 14 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 14 to about 18 months prior, at least about 14 to about 17 months prior, at least about 14 to about 16 months prior, or at least about 14 to about 15 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 15 to about 18 months prior, at least about 15 to about 17 months prior, or at least about 15 to about 16 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 16 to about 18 months prior, or at least about 16 to about 17 months prior.In a specific embodiment, the subject is determined to have received a stem cell transplant at least about 17 months to about 18 months previously.

[0357] In another specific embodiment, the subject is determined to have been administered a stem cell transplant at least about 8 or 9 months to about 14 months, at least about 8 or 9 months to about 13 months, at least about 8 or 9 months to about 12 months, at least about 8 or 9 months to about 11 months, at least about 8 or 9 months to about 10 months, at least about 9 months to about 15 or 16 months, at least about 10 months to at least about 15 or 16 months, at least about 11 months to at least about 15 or 16 months, at least about 12 months to at least about 15 or 16 months, or at least about 13 months to at least about 15 or 16 months. In another specific embodiment, the subject is determined to have been administered a stem cell transplant at least about 8 or 9 months to about 12 months. In another specific embodiment, the subject is determined to have been administered a stem cell transplant at least about 9 months to at least about 15 or 16 months. In another specific embodiment, the subject has been determined to have received a stem cell transplant at least about 12 months to at least about 15 or 16 months previously.

[0358] In certain embodiments, the cancer is leukemia. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, and the high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0359] In certain embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, e.g., or allogeneic stem cell transplant followed by autologous stem cell transplant). In a specific embodiment, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In a specific embodiment, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In a specific embodiment, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In a specific embodiment, the stem cell transplant is autologous stem cell transplant. In a specific embodiment, the stem cell transplant is allogeneic stem cell transplant.

[0360] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0361] In certain embodiments, the subject is a human.

[0362] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02 scFv, e.g., SEQ ID NO: 38.

[0363] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0364] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0365]

[0010] In another aspect, provided herein is a method of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need thereof, wherein the subject has received a stem cell transplant (SCT), the method comprising administering to the subject chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) prepared from peripheral blood mononuclear cells (PBMCs) isolated from the patient, wherein, at the time the PBMCs are isolated, the subject last received a stem cell transplant at least about 6 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last received a stem cell transplant at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent a stem cell transplant at least about 9 months prior to the time the PBMCs are isolated, hi certain embodiments, the subject last underwent a stem cell transplant at least about 12 months prior to the time the PBMCs are isolated.

[0366] In another aspect, provided herein is a method of treating cancer caused by cells expressing B-cell maturation antigen (BCMA) in a subject in need thereof, wherein the subject has undergone stem cell transplantation (SCT), the method comprising administering to the subject chimeric antigen receptor (CAR) T cells against BCMA (BCMA CAR T cells) prepared from peripheral blood mononuclear cells (PBMCs) isolated from the patient, wherein, at the time the PBMCs are isolated, the subject last underwent an SCT at least about 9 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent an SCT at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months prior to the time the PBMCs are isolated. In certain embodiments, the subject last underwent an SCT at least about 12 months prior to the time the PBMCs are isolated.

[0367] In specific embodiments, the subject last underwent stem cell transplantation (SCT) at least about 6 months to about 18 months, at least about 6 months to about 17 months, at least about 6 months to about 16 months, at least about 6 months to about 15 months, at least about 6 months to about 14 months, at least about 6 months to about 13 months, at least about 6 months to about 12 months, at least about 6 months to about 11 months, at least about 6 months to about 10 months, at least about 6 months to about 9 months, at least about 6 months to about 8 months, or at least about 6 months to about 7 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 7 months to about 18 months, at least about 7 months to about 17 months, at least about 7 months to about 16 months, at least about 7 months to about 15 months, at least about 7 months to about 14 months, at least about 7 months to about 13 months, at least about 7 months to about 12 months, at least about 7 months to about 11 months, at least about 7 months to about 10 months, at least about 7 months to about 9 months, or at least about 7 months to about 8 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 8 months to about 18 months, at least about 8 months to about 17 months, at least about 8 months to about 16 months, at least about 8 months to about 15 months, at least about 8 months to about 14 months, at least about 8 months to about 13 months, at least about 8 months to about 12 months, at least about 8 months to about 11 months, at least about 8 months to about 10 months, or at least about 8 months to about 9 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 9 months to about 18 months, at least about 9 months to about 17 months, at least about 9 months to about 16 months, at least about 9 months to about 15 months, at least about 9 months to about 14 months, at least about 9 months to about 13 months, at least about 9 months to about 12 months, at least about 9 months to about 11 months, or at least about 9 months to about 10 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 9 months to about 15 months prior.In specific embodiments, the subject is determined to have received a stem cell transplant at least about 9 months to about 12 months prior. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 10 months to about 18 months, at least about 10 months to about 17 months, at least about 10 months to about 16 months, at least about 10 months to about 15 months, at least about 10 months to about 14 months, at least about 10 months to about 13 months, at least about 10 months to about 12 months, or at least about 10 months to about 11 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 11 to about 18 months, at least about 11 to about 17 months, at least about 11 to about 16 months, at least about 11 to about 15 months, at least about 11 to about 14 months, at least about 11 to about 13 months, or at least about 11 to about 12 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 12 to about 18 months, at least about 12 to about 17 months, at least about 12 to about 16 months, at least about 12 to about 15 months, at least about 12 to about 14 months, or at least about 12 to about 13 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 12 to about 15 months prior to the time PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 13 to about 18 months, at least about 13 to about 17 months, at least about 13 to about 16 months, at least about 13 to about 15 months, or at least about 13 to about 14 months prior to the time PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 14 to about 18 months, at least about 14 to about 17 months, at least about 14 to about 16 months, or at least about 14 to about 15 months prior to the time PBMCs are isolated.In specific embodiments, the subject is determined to have received a stem cell transplant at least about 15 months to about 18 months, at least about 15 months to about 17 months, or at least about 15 months to about 16 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 16 months to about 18 months, or at least about 16 months to about 17 months prior to the time the PBMCs are isolated. In specific embodiments, the subject is determined to have received a stem cell transplant at least about 17 months to about 18 months prior to the time the PBMCs are isolated.

[0368] In another specific embodiment, the subject last underwent a stem cell transplant at least about 8 or 9 months to about 14 months before the time the PBMCs are isolated, at least about 8 or 9 months to about 13 months before the time the PBMCs are isolated, at least about 8 or 9 months to about 12 months before the time the PBMCs are isolated, at least about 8 or 9 months to about 11 months before the time the PBMCs are isolated, at least about 8 or 9 months to about 10 months before the PBMCs are isolated, at least about 9 months to about 15 or 16 months before the time the PBMCs are isolated, at least about 10 months to at least about 15 or 16 months before the PBMCs are isolated, at least about 11 months to at least about 15 or 16 months before the PBMCs are isolated, at least about 12 months to at least about 15 or 16 months before the PBMCs are isolated, or at least about 13 months to at least about 15 or 16 months before the PBMCs are isolated. In another specific embodiment, the subject received their last stem cell transplant at least about 8 or 9 months to about 12 months before the time the PBMCs are isolated. In another specific embodiment, the subject received their last stem cell transplant at least about 9 months to at least about 15 or 16 months before the time the PBMCs are isolated. In another specific embodiment, the subject received their last stem cell transplant at least about 12 months to at least about 15 or 16 months before the time the PBMCs are isolated.

[0369] In certain embodiments, the cancer is leukemia. In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, and the high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0370] In certain embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In a specific embodiment, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In a specific embodiment, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In a specific embodiment, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In a specific embodiment, the stem cell transplant is autologous stem cell transplant. In a specific embodiment, the stem cell transplant is allogeneic stem cell transplant.

[0371] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0372] In certain embodiments, the subject is a human.

[0373] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02 scFv, e.g., SEQ ID NO: 38.

[0374] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0375] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0376] In certain embodiments, the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma. In certain embodiments, the cancer is multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma or relapsed and / or refractory multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma. In certain embodiments, the multiple myeloma is high-risk multiple myeloma, where high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse. In certain embodiments, the multiple myeloma is not R-ISS stage III disease. In certain embodiments, the multiple myeloma is relapsed and / or refractory multiple myeloma.

[0377] In certain embodiments, the stem cell transplant is one or more of autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, and tandem stem cell transplant (e.g., double autologous stem cell transplant, double allogeneic stem cell transplant, autologous stem cell transplant followed by allogeneic stem cell transplant, or allogeneic stem cell transplant followed by autologous stem cell transplant). In a specific embodiment, the SCT is autologous stem cell transplant, allogeneic stem cell transplant, syngeneic stem cell transplant, or tandem stem cell transplant. In a specific embodiment, the stem cell transplant is one or more of bone marrow transplant, peripheral blood stem cell transplant, and umbilical cord blood stem cell transplant. In a specific embodiment, the SCT is bone marrow transplant, peripheral blood stem cell transplant, or umbilical cord blood stem cell transplant. In a specific embodiment, the stem cell transplant is autologous stem cell transplant. In a specific embodiment, the stem cell transplant is allogeneic stem cell transplant.

[0378] In certain embodiments, the manufactured T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor-infiltrating lymphocytes (TILs). In certain embodiments, the manufactured T cells are chimeric antigen receptor (CAR) T cells. In certain embodiments, the manufactured T cells are one or more of tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, and tumor-infiltrating lymphocytes (TILs).

[0379] In certain embodiments, the subject is a human.

[0380] In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises an antibody or antibody fragment that targets BCMA. In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a single-chain Fv antibody or antibody fragment (scFv). In certain embodiments, the BCMA CAR T cells comprise a CAR against BCMA, wherein the CAR against BCMA comprises a BCMA02 scFv, e.g., SEQ ID NO: 38. In certain embodiments, the BCMA CAR T cells are idecactogen bicleucel cells. In certain embodiments, the BCMA CAR T cells are ABECMA® cells (cells used in ABECMA® immunotherapy). In certain embodiments, the BCMA CAR T cells are siltacactogen autocleucel cells. In certain embodiments, the BCMA CAR T cells are CARVYKTI™ cells (cells used in CARVYKTI™ immunotherapy).

[0381] In certain embodiments, prior to administering the BCMA CAR T cells to the subject, the subject undergoes an apheresis procedure, for example a leukapheresis procedure, to collect PBMCs for the manufacture of BCMA CAR T cells.

[0382] In certain embodiments, the BCMA CAR T cells are administered by intravenous infusion.

[0383] In another aspect, provided herein are methods of producing T cells (e.g., CAR T cells) from a subject, the methods comprising: (a) administering stem cell transplantation (SCT) to the subject as part of a tumor or cancer treatment; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 6 months after step (a); and then (c) producing T cells (e.g., CAR T cells) from the PBMCs. In certain embodiments, step (b) is performed at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a). In certain embodiments, step (b) is performed at least about 9 months after step (a). In certain embodiments, step (b) is performed at least about 12 months after step (a).

[0384] In another aspect, provided herein is a method of producing T cells (e.g., CAR T cells) from a subject, the method comprising: (a) administering to the subject a stem cell transplant (SCT) to treat a tumor or cancer; (b) isolating peripheral blood mononuclear cells (PBMCs) from the subject at least about 9 months after step (a); and then (c) producing the T cells from the PBMCs. In certain embodiments, step (b) is performed at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, or at least about 18 months after step (a). In certain embodiments, step (b) is performed at least about 12 months after step (a).

[0385] In specific embodiments, step (b) is performed at least about 6 months to about 18 months after step (a), at least about 6 months to about 17 months after step (a), at least about 6 months to about 16 months after step (a), at least about 6 months to about 15 months after step (a), at least about 6 months to about 14 months after step (a), at least about 6 months to about 13 months after step (a), at least about 6 months to about 12 months after step (a), at least about 6 months to about 11 months after step (a), at least about 6 months to about 10 months after step (a), at least about 6 months to about 9 months after step (a), at least about 6 months to about 8 months after step (a), or at least about 6 months to about 7 months after step (a). In specific embodiments, step (b) is performed at least about 7 months to about 18 months after step (a), at least about 7 months to about 17 months after step (a), at least about 7 months to about 16 months after step (a), at least about 7 months to about 15 months after step (a), at least about 7 months to about 14 months after step (a), at least about 7 months to about 13 months after step (a), at least about 7 months to about 12 months after step (a), at least about 7 months to about 11 months after step (a), at least about 7 months to about 10 months after step (a), at least about 7 months to about 9 months after step (a), or at least about 7 months to about 8 months after step (a). In specific embodiments, step (b) is performed at least about 8 months to about 18 months after step (a), at least about 8 months to about 17 months after step (a), at least about 8 months to about 16 months after step (a), at least about 8 months to about 15 months after step (a), at least about 8 months to about 14 months after step (a), at least about 8 months to about 13 months after step (a), at least about 8 months to about 12 months after step (a), at least about 8 months to about 11 months after step (a), at least about 8 months to about 10 months after step (a), or at least about 8 months to about 9 months after step (a).In specific embodiments, step (b) is performed at least about 9 months to about 18 months after step (a), at least about 9 months to about 17 months after step (a), at least about 9 months to about 16 months after step (a), at least about 9 months to about 15 months after step (a), at least about 9 months to about 14 months after step (a), at least about 9 months to about 13 months after step (a), at least about 9 months to about 12 months after step (a), at least about 9 months to about 11 months after step (a), or at least about 9 months to about 10 months after step (a). In specific embodiments, step (b) is performed at least about 9 months to about 15 months after step (a). In specific embodiments, step (b) is performed at least about 9 months to about 12 months after step (a). In specific embodiments, step (b) is performed at least about 10 months to about 18 months after step (a), at least about 10 months to about 17 months after step (a), at least about 10 months to about 16 months after step (a), at least about 10 months to about 15 months after step (a), at least about 10 months to about 14 months after step (a), at least about 10 months to about 13 months after step (a), at least about 10 months to about 12 months after step (a), or at least about 10 months to about 11 months after step (a). In specific embodiments, step (b) is performed at least about 11 to about 18 months after step (a), at least about 11 to about 17 months after step (a), at least about 11 to about 16 months after step (a), at least about 11 to about 15 months after step (a), at least about 11 to about 14 months after step (a), at least about 11 to about 13 months after step (a), or at least about 11 to about 12 months after step (a). In specific embodiments, step (b) is performed at least about 12 to about 18 months after step (a), at least about 12 to about 17 months after step (a), at least about 12 to about 16 months after step (a), at least about 12 to about 15 months after step (a), at least about 12 to about 14 months after step (a), or at least about 12 to about 13 months after step (a). In a specific embodiment, step (b) occurs at least about 12 months to about 15 months after step (a).In specific embodiments, step (b) is performed at least about 13 to about 18 months after step (a), at least about 13 to about 17 months after step (a), at least about 13 to about 16 months after step (a), at least about 13 to about 15 months after step (a), or at least about 13 to about 14 months after step (a). In specific embodiments, step (b) is performed at least about 14 to about 18 months after step (a), at least about 14 to about 17 months after step (a), at least about 14 to about 16 months after step (a), or at least about 14 to about 15 months after step (a). In specific embodiments, step (b) is performed at least about 15 to about 18 months...

Claims

1. 1. A composition for use in a method of treating a tumor or cancer in a subject in need of such treatment, comprising T cells, wherein the subject has previously undergone stem cell transplantation (SCT) as part of the treatment of the tumor or cancer, and the T cells are derived from peripheral blood mononuclear cells (PBMCs) isolated from the subject; (a) the subject has previously undergone SCT at least about 9 months prior to said isolation; (b) the isolating occurs at least about 9 months after the subject has undergone SCT; and / or (c) wherein at the time of said isolation, said subject has been determined to have been administered SCT at least about 9 months prior.

2. The composition of claim 1, further characterized in that the subject is determined to have not been administered SCT in less than about 9 months prior to said isolation.

3. The tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenal cortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, Wilms' tumor , glioblastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large cell Alveolar B-cell lymphoma, Intravascular large B-cell lymphoma, Primary effusion lymphoma, Burkitt's lymphoma, T-lymphocytic prolymphocytic leukemia, Acute myeloid leukemia (AML), Acute lymphocytic leukemia (ALL), Chronic myeloid leukemia (CML), Juvenile chronic myeloid leukemia (JCML), Juvenile myelomonocytic leukemia (JMML), T-lymphocytic large granular lymphocytic leukemia, Aggressive NK cell leukemia, Adult T-lymphocytic leukemia / lymphoma, Nodal 3. The composition of claim 1 or 2, wherein the tumor is selected from the group consisting of exogenous NK / T lymphocytic lymphoma, nasal type, enteropathy type T lymphocytic lymphoma, hepatosplenic T lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sezary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T lymphocytic lymphoma, peripheral T lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, and multiple myeloma.

4. wherein the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma, and optionally (a) the cancer is non-Hodgkin's lymphoma, and the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma; or (b) the cancer is multiple myeloma, optionally the multiple myeloma is (i) high-risk multiple myeloma, optionally wherein said high-risk multiple myeloma is R-ISS stage III disease and / or disease characterized by early relapse; or (ii) Relapsed and / or refractory multiple myeloma.

5. The composition of any one of claims 1, 2 and 4, wherein the SCT is autologous stem cell transplantation, allogeneic stem cell transplantation, syngeneic stem cell transplantation, tandem stem cell transplantation, bone marrow transplantation, peripheral blood stem cell transplantation, or umbilical cord blood stem cell transplantation.

6. 5. The composition of any one of claims 1, 2 and 4, wherein the T cells are tumor-specific T cells, chimeric antigen receptor (CAR) T cells, engineered T cell receptor (TCR) T cells, or tumor infiltrating lymphocytes (TILs).

7. 2. The composition of claim 1, wherein the subject is undergoing an apheresis procedure to collect PBMCs, optionally wherein the apheresis procedure is a leukapheresis procedure.

8. The composition according to any one of claims 1, 2 and 4, characterized in that the T cells are used to be administered by intravenous infusion.

9. The composition of any one of claims 1, 2 and 4, wherein the subject is a human.

10. The composition of any one of claims 1, 2 and 4, wherein the tumor or cancer is caused by cells expressing B-cell maturation antigen (BCMA).

11. 2. The composition of claim 1, wherein the T cell is a chimeric antigen receptor (CAR) T cell, and optionally the CART T cell is a CAR T cell directed against BCMA (BCMA CAR T cell), and optionally the BCMA CAR T cell comprises an antibody or antibody fragment, or a single chain Fv antibody or antibody fragment (scFv), that targets BCMA.

12. The composition of claim 11, wherein the chimeric antigen receptor (CAR) comprises an extracellular antigen-binding domain that binds BCMA, a transmembrane domain, and an intracellular signaling region.

13. 13. The composition of claim 12, wherein the intracellular signaling region further comprises a costimulatory signaling domain, optionally wherein the costimulatory signaling domain comprises the intracellular signaling domain of CD28, 4-1BB, or ICOS, or a signaling portion thereof.

14. The composition of claim 13, wherein the costimulatory signaling domain is between the transmembrane domain and the cytoplasmic signaling domain of the CD3-zeta (CD3ζ) chain.

15. The composition of claim 12, wherein the transmembrane domain is or comprises a transmembrane domain from CD28 or CD8, optionally human CD28 or CD8.

16. The chimeric antigen receptor (CAR) further comprises an extracellular spacer between the antigen-binding domain and the transmembrane domain, and optionally (a) the spacer is from CD8; (b) the spacer is a CD8α hinge, and / or (c) the transmembrane domain and spacer are from CD8.

17. The composition of claim 11 , wherein the BCMA CAR T cell comprises SEQ ID NO:

38.

18. The composition of claim 11, wherein the BCMA CAR T cells are idecabutagen biculeucel cells or siltacabtagene autoreucel cells.

19. 1. A composition comprising T cells that shortens the time to recovery from thrombocytopenia following T cell therapy in a subject, wherein the T cells are derived from peripheral blood mononuclear cells (PBMCs) isolated from the subject, and the subject has previously undergone stem cell transplantation (SCT) at least about 9 months prior to the isolation.

20. 1. A method of producing T cells from a subject, comprising producing T cells from peripheral blood mononuclear cells (PBMCs) isolated from the subject, wherein at least 9 months prior to said isolation, the subject has previously undergone stem cell transplantation (SCT) as part of a treatment for a tumor or cancer.

21. (a) the subject has previously undergone SCT at least about 9 months prior to step (a); (b) the isolating occurs at least about 9 months after the subject has undergone SCT; and / or (c) at the time of said isolation, said subject has been determined to have been administered SCT at least about 9 months prior.

22. 21. The method of claim 20, further comprising determining that the subject has not been administered SCT in less than about 9 months prior to said isolation.

23. The tumor or cancer is lymphoma, lung cancer, breast cancer, prostate cancer, liver cancer, cholangiocarcinoma, glioma, colon adenocarcinoma, myelodysplasia, adrenal cortical carcinoma, thyroid cancer, nasopharyngeal carcinoma, melanoma, skin cancer, colorectal cancer, desmoid tumor, desmoplastic small round cell tumor, endocrine tumor, Ewing's sarcoma, peripheral primitive neuroectodermal tumor, solid germ cell tumor, hepatoblastoma, neuroblastoma, non-rhabdomyosarcoma soft tissue sarcoma, osteosarcoma, retinoblastoma, rhabdomyosarcoma, Wilms' tumor, glioblastoma, gli ... Blastoma, myxoma, fibroma, lipoma, chronic lymphocytic leukemia (small lymphocytic lymphoma), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, Waldenström's macroglobulinemia, splenic marginal zone lymphoma, plasma cell myeloma, plasmacytoma, extranodal marginal zone B-cell lymphoma, MALT lymphoma, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma Cell Lymphoma, Intravascular Large B-cell Lymphoma, Primary Effusion Lymphoma, Burkitt's Lymphoma, T-lymphocytic Prolymphocytic Leukemia, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Chronic Myelogenous Leukemia (CML), Juvenile Chronic Myelogenous Leukemia (JCML), Juvenile Myelomonocytic Leukemia (JMML), T-lymphocytic Large Granular Lymphocyte Leukemia, Aggressive NK Cell Leukemia, Adult T-lymphocytic Leukemia / Lymphoma, Extranodal NK / 23. The method of any one of claims 20 to 22, wherein the tumor is T-lymphocytic lymphoma, nasal type, enteropathy-type T-lymphocytic lymphoma, hepatosplenic T-lymphocytic lymphoma, blastic NK cell lymphoma, mycosis fungoides, Sezary syndrome, primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, angioimmunoblastic T-lymphocytic lymphoma, peripheral T-lymphocytic lymphoma (unspecified), anaplastic large cell lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, or multiple myeloma.

24. wherein the cancer is multiple myeloma, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma, and optionally (a) the cancer is non-Hodgkin's lymphoma, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), diffuse large B-cell lymphoma, follicular lymphoma, immunoblastic large cell lymphoma, precursor B-lymphoblastic lymphoma, or mantle cell lymphoma; or (b) the cancer is multiple myeloma, optionally the multiple myeloma is (i) high-risk multiple myeloma, wherein the high-risk multiple myeloma is R-ISS stage III disease and / or a disease characterized by early relapse; or (ii) The method of claim 20, wherein the patient has relapsed and / or refractory multiple myeloma.

25. 25. The method of any one of claims 20 to 22 and 24, wherein the SCT is autologous stem cell transplantation, allogeneic stem cell transplantation, syngeneic stem cell transplantation, tandem stem cell transplantation, bone marrow transplantation, peripheral blood stem cell transplantation, or umbilical cord blood stem cell transplantation.

26. 25. The method of any one of claims 20-22 and 24, wherein the produced T cells are tumor-specific T cells, chimeric antigen receptor T cells (CAR T cells), engineered T cell receptor (TCR) T cells, or tumor infiltrating lymphocytes (TILs).

27. 21. The method of claim 20, comprising introducing a recombinant nucleic acid encoding a chimeric antigen receptor (CAR) into PBMCs or T cells isolated from a leukapheresis sample.

28. 28. The method of claim 27, wherein said introducing is by transduction with a viral vector comprising a recombinant nucleic acid encoding a CAR, optionally wherein said viral vector is a lentiviral vector.

29. 28. The method of claim 27, wherein prior to said introducing, said producing further comprises stimulating the composition of T cells with an agent capable of activating T cells, optionally said agent comprising an anti-CD3 antibody and / or an anti-CD28 antibody.

30. 28. The method of claim 27, wherein the producing further comprises expanding a cell into which a recombinant nucleic acid encoding a chimeric antigen receptor (CAR) has been introduced.

31. 28. The method of claim 27, wherein the CART T cell is a CAR T cell against BCMA (BCMA CAR T cell), and the BCMA CAR T cell comprises an antibody or antibody fragment, or a single chain Fv antibody or antibody fragment (scFv), that targets BCMA.

32. 28. The method of claim 27, wherein the chimeric antigen receptor (CAR) comprises an extracellular antigen-binding domain that binds BCMA, a transmembrane domain, and an intracellular signaling region.

33. 33. The method of claim 32, wherein the intracellular signaling region further comprises a costimulatory signaling domain, optionally wherein the costimulatory signaling domain comprises the intracellular signaling domain of CD28, 4-1BB, or ICOS, or a signaling portion thereof.

34. The method of claim 33, wherein the costimulatory signaling domain is between the transmembrane domain and the cytoplasmic signaling domain of the CD3-zeta (CD3ζ) chain.

35. 34. The method of claim 33, wherein the transmembrane domain is or comprises a transmembrane domain from CD28 or CD8, optionally a transmembrane domain from human CD28 or CD8.

36. The CAR further comprises an extracellular spacer between the antigen-binding domain and the transmembrane domain, and optionally (a) the spacer is from CD8; (b) the spacer is a CD8α hinge, and / or (c) the transmembrane domain and spacer are from CD8.

37. 33. The method of claim 32, wherein the BCMA CAR T cell comprises SEQ ID NO:

38.

38. 32. The method of claim 31 , wherein the BCMA CAR T cells are idecabutagen biculeucel cells or siltacabtagene autoreucel cells.

39. 21. The method of claim 20, wherein prior to administering the T cells to the subject, the subject undergoes an apheresis procedure to collect PBMCs for the manufacture of T cells, optionally the apheresis procedure is a leukapheresis procedure.

40. 40. The method of any one of claims 20 to 22, 24 and 27 to 39, characterized in that the T cells or BCMA CAR T cells are used to be administered by intravenous infusion.

41. 40. The method of any one of claims 20-22, 24, and 27-39, wherein the subject is a human.

42. 1. Use of T cells in the manufacture of a medicament for treating a tumor or cancer in a subject, wherein the subject has previously undergone stem cell transplantation (SCT) for the treatment of the tumor or cancer, and wherein the medicament is manufactured by a method comprising producing the T cells from peripheral blood mononuclear cells (PBMCs) isolated from the subject.

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