New recombinant nucleic acid molecule encoding chimeric antigen receptor comprising a single chain antibody or single chain antibody fragment, for treating subject having disease associated with expression of B-cell maturation antigen, where disease is multiple myeloma and non-Hodgkin's lymphoma
	KARULKAR A A; KHAN A N; PURWAR R K
	2024-03-16
专利权人	IMMUNOADOPTIVE CELL THERAPY PRIVATE LTD (IMMU-Non-standard) ; INDIAN INST TECHNOLOGY BOMBAY (IITB-C)
申请日期	2024-03-16
专利号	IN202421019457-A
成果简介	NOVELTY - Recombinant nucleic acid molecule encoding a chimeric antigen receptor (CAR) is new, where recombinant nucleic acid molecule comprises: (a) a single chain antibody or single chain antibody fragment comprising an anti-BCMA binding domain, where the anti-BCMA binding domain is a murine anti-BCMA binding domain or a humanized anti-BCMA binding domain; (b) a hinge region; (c) a transmembrane domain; and (d) a cytoplasmic domain comprising a costimulatory domain and a signaling domain. The anti-BCMA binding domain is an single-chain variable fragment (scFv) comprising a Heavy chain variable region (HCVR) and a light chain variable region (LCVR) attached by a linker. USE - Recombinant nucleic acid molecule encoding a chimeric antigen receptor used in kit and pharmaceutical composition for preparing immune cells expressing an anti-B-cell maturation antigen chimeric antigen receptor, and treating subject having a disease associated with expression of BCMA, where disease associated with BCMA expression is selected from multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL), Chronic lymphocytic leukemia (CLL), systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, autoimmune hemolytic anemia, idiopathic thrombocytopenia purpura, anti-phospholipid syndrome, Chagas' disease, Grave's disease, Wegener's granulomatosis, poly-arteritis nodosa, Sjogren's syndrome, pemphigus vulgaris, scleroderma, multiple sclerosis, anti-phospholipid syndrome, ANCA associated vasculitis, Goodpasture's disease, Kawasaki disease, and rapidly progressive glomerulonephritis (claimed). No biological data given. ADVANTAGE - The immune cell shows immune response either in antibody production, or activation of specific immunologically-competent cells, or both. The pharmaceutical composition enhances the overall safety profile of the treatment, enabling more effective therapeutic outcomes while minimizing potential risks. The anti-BCMA CAR construct anti-BCMA binding domain having human antibody-based framework region contribute significantly to the advancement of CAR-T cell therapy. The recombinant nucleic acid molecule encoding chimeric antigen receptor shows good safety, efficacy, toxicity, and immunogenicity of the CAR-T cells. DETAILED DESCRIPTION - Recombinant nucleic acid molecule encoding a chimeric antigen receptor (CAR) is new, where recombinant nucleic acid molecule comprises: (a) a single chain antibody or single chain antibody fragment comprising an anti-BCMA binding domain, where the anti-BCMA binding domain is a murine anti-BCMA binding domain or a humanized anti-BCMA binding domain; (b) a hinge region; (c) a transmembrane domain; and (d) a cytoplasmic domain comprising a costimulatory domain and a signaling domain. The anti-BCMA binding domain is a single-chain variable fragment (scFv) comprising a Heavy chain variable region (HCVR) and a light chain variable region (LCVR) attached by a linker. The HCVR comprises a heavy chain complementarity determining region 1 (HC CDR1) having nucleotide sequence comprising 30 nucleobases ggctacaccttcaccgactacagcatcaac of (SEQ ID NO: 54), heavy chain complementarity determining region 2 (HCCDR2) having nucleotide sequence comprising 51 nucleobases of (SEQ ID NO: 55), given in the specification, heavy chain complementarity determining region 3 (HCCDR3) having nucleotide sequence comprising 24 nucleobases gattacagctacgccatggattat or gacttcagctacgccatggattat of SEQ ID NO: 56 or 108 and LCVR comprises a light chain complementarity determining region 1 (LC CDR1) having the nucleotide sequence comprising 45 nucleobases of SEQ ID NO: 8 or 46 nucleobases of SEQ ID NO: 100, light chain complementarity determining region 2 (LCCDR2) having the nucleotide sequence compising 21 nucleobases ctggcctctaatgtgcagaca of SEQ ID NO: 39, and light chain complementarity determining region 3 (LCCDR3) having the nucleotide sequence comprising 27 nucleobases ctgcagagcagaacaatccccagaacc and ctgcagagccggaccatcatcagaacc of SEQ ID NO: 40 or 101. INDEPENDENT CLAIMS are included for: Chimeric antigen receptor (CAR) polypeptide, which comprises: (a) a single chain antibody or single chain antibody fragment comprising an anti-BCMA binding domain; Vector, which comprises the nucleic acid molecule; Kit, which comprises a vector encoding the nucleic acid molecule and reagents for immune cell activation, expansion, and engineering; Fusion recombinant protein, which comprises an anti-BCMA binding domain (scFv) fused to a constant region of an antibody (Fc), where the scFv-Fc construct has a nucleotide sequence selected from sequences comprising 4977 nucleobases of (SEQ ID NOs: 125, 127, 129, 131 and 133), given in the specification and encoding 515 amino acid sequence (SEQ ID NO: 124, 126, 128, 130 and 132), given in the specification; Immune cell, which comprises the vector or expressing the CAR polypeptide; and Pharmaceutical composition, which comprises the recombinant nucleic acid molecule or CAR polypeptide or vector or immune cell, with a pharmaceutically acceptable carrier, diluent, or excipient, and further pharmaceutically active polypeptides and/or compounds; Method of preparing an anti-B-cell maturation antigen (BCMA) CAR encoded by the nucleic acid, which involves transducing a T cell with a vector; Method for preparing immune cells expressing an anti-BCMA CAR encoded by a nucleic acid, which involves: (i) providing a population of immune cells; (ii) introducing into the immune cells a nucleic acid; and (iii) culturing the immune cells under conditions allowing for expression of the chimeric receptor; Method for manufacturing T cells expressing an anti-BCMA chimeric antigen receptor (CAR), which involves: (1) isolation and selection of immune cells from a human donor; (2) enriching CD3+ T cells from the immune cells using magnetic bead separation; (3) activating the enriched CD3+ T cells by anti-CD3/anti-CD28 antibodies in a culture medium comprising recombinant interleukin-2 (IL-2) at 37℃ with 5 vol.% carbon dioxide (CO2) for 36-40 hours; (d) transducing the activated T cells with a lentiviral vector encoding an anti-BCMA CAR, at a multiplicity of infection (MOI) of up to 10, and incubating the transduced cells at 37℃ with 5 vol.% CO2 for 24-30 hours; and (e) expanding the transduced T cells to obtain a population of T cells expressing the anti-BCMA CAR on their cell surface at a transduction efficiency of 10%; and Method of treating a subject having a disease associated with expression of BCMA, which involves administering to the subject an effective amount of an immune effector cell.
IPC 分类号	A61K-039/00 ; A61P-035/00 ; C07K-014/725 ; C07K-016/28 ; C12N-005/0783
国家	印度
专业领域	医药卫生
语种	英语
成果类型	专利
文献类型	科技成果
条目标识符	http://119.78.100.226:8889/handle/3KE4DYBR/17685
专题	中国科学院新疆生态与地理研究所
作者单位	1.IMMUNOADOPTIVE CELL THERAPY PRIVATE LTD (IMMU-Non-standard) 2.INDIAN INST TECHNOLOGY BOMBAY (IITB-C)
推荐引用方式 GB/T 7714	KARULKAR A A,KHAN A N,PURWAR R K. New recombinant nucleic acid molecule encoding chimeric antigen receptor comprising a single chain antibody or single chain antibody fragment, for treating subject having disease associated with expression of B-cell maturation antigen, where disease is multiple myeloma and non-Hodgkin's lymphoma. IN202421019457-A[P]. 2024.

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