A bispecific chimeric antigen receptor gene targeting MLL leukemia and its application

Abstract

The invention relates to a gene of an MLL leukemia targeted dual-specific chimeric antigen receptor and an application of the MLL leukemia targeted dual-specific chimeric antigen receptor. The dual-specific chimeric antigen receptor disclosed by the invention can be used for specifically recognizing two kinds of tumor associated antigens, i.e., CD19 and CD133 on surfaces of MLL leukemia cells. The dual-specific chimeric antigen receptor is expressed through recombining a TanCAR molecule to a virus vector and carrying out T lymphocyte series transfection, dual positive tumor cells, i.e., the CD19 and the CD133 can be specifically recognized and killed, the kill effect on non-tumor cells is relieved, and the probability of escape of tumor antigens is lowered. The MLL leukemia cells can be specifically killed by TanCAR(1linker)-Jurkat in case of a relatively low effector-target ratio, and toxic or side effects less occur in subsequent clinical use, for example cytokine storm and neurotoxicity. The dual-specific chimeric antigen receptor disclosed by the invention can be applied to the treatment of MLL leukemia and is used for clearing in-vivo tumors from patients and prolonging lifetime of the patients.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a bispecific chimeric antigen receptor gene targeting MLL leukemia. Background technique [0002] The immune response mediated by tumor-specific T cells is the main means for the body to eliminate tumor cells. In a normal immune response, T cell activation requires two stimulating signals. Among them, the TCR-CD3 complex on the surface of T cells binds to antigen peptide-MHC molecules, providing the first signal for T cell activation and determining the killing specificity of T cells; the second signal is formed by T cells and antigen-presenting cells (APCs). or other co-stimulatory molecules on the cell surface. Tumor cells produce immune escape by down-regulating the expression of molecules involved in T cell recognition and antigen response, reducing immunogenicity, etc., so that the body's immune system cannot clear the tumor well. [0003] Studies have found that the s...

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Problems solved by technology

However, since CD19 is a surface marker of B cells and is expressed in both normal B cells and B cell tumors, this treatment strategy will inevitably bring about a side effect of reducing normal B cells. There is a great degree of remission or complete cure, but long-term or even lifelong intravenous gamma globulin supplementation is required to avoid the decline in immunity caused by the reduction of B cells, which greatly reduces the quality of life of patients

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