Chimeric antigen receptor targeting CD22 and application for chimeric antigen receptor

Abstract

The invention discloses a chimeric antigen receptor targeting CD22 and an application for the chimeric antigen receptor. The chimeric antigen receptor has a sequence selected from one of the followingtwo structures: a first structure, which comprises a CD22 antigen binding domain and a constant domain of a T cell receptor (TCR); and a second structure, which comprises a transmembrane protein signal peptide, a CD22 antigen binding structural domain, a CD8 protein molecule hinge region, a transmembrane region, a 4-1BB costimulatory structural domain and a CD3<zeta> intracellular signal transduction structural domain which are sequentially connected in series. Compared with a traditional CD28, 4-1BB costimulatory structural domain, the chimeric antigen receptor provided by the invention shows more persistent anti-tumor activity, can be combined with CD19 chimeric antigen receptor T cells for sequential application, improves the coverage rate of CART cells on tumor cells, or is applied totreatment of leukemia negative recurrence by being combined with the CD19 chimeric antigen receptor T cells, and has good application prospect in treatment of blood and lymphatic system malignant tumors.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a chimeric antigen receptor targeting CD22 and its application. Background technique [0002] Adoptive cell therapy (ACT) refers to the isolation of immunocompetent cells from tumor patients, expansion and functional identification in vitro, and then reinfusion to patients, so as to directly kill tumors or stimulate the body's immune response to kill tumor cells. [0003] Immunotherapy is the fourth cancer treatment after surgery, radiotherapy and chemotherapy. Chimeric antigen receptor (chimeric antigen receptor, CAR) T-cell technology is a recently rapidly developed cellular immunotherapy technology. CAR is an artificially synthesized fusion receptor, which includes an extracellular antigen-binding region and a transmembrane region in structure. , intracellular signal transduction region and co-stimulatory signal region. The extracellular region is a monoclonal antibody ...

AI Technical Summary

Problems solved by technology

[0009] Exogenously transferred TCR molecules, on the one hand, the exogenous TCR molecules may be mismatched with the endogenous TCR molecule α-chain and β-chain. Since there is no negative selection by the thymus, the mismatch of TCR molecules may cause these modified T cells to self-tissue. On the other hand, in terms of interacting with the CD3 complex, exogenous TCR molecules may compete with endogenous TCR molecules, affecting the assembly of TCR-CD3 complexes, affecting T cell activation signal transduction, and ultimately affecting T cells Function

[0010] After all, the artificially synthesized activation signal of the fusion of the antigen recognition region and the activation domain is different from the signal transmitted by the endogenous TCR-CD3 complex. On the one hand, the artificially synthesized CAR T cell activation signal will easily lead to T cell exhaustion. On the one hand, a large number of cytokines are sometimes produced in the patient's body, causing a cytokine storm, and in severe cases, it will cause the death of the patient.

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