OCTS-CAR double-targeting chimeric antigen receptor, coding gene, recombinant expression vector and establishment and application of OCTS-CAR double-targeting chimeric antigen receptor, coding gene and recombinant expression vector

Abstract

The invention provides an OCTS-CAR technique-based OCTS-CAR double-targeting chimeric antigen receptor, a coding gene and a recombinant expression vector and establishment and application of the OCTS-CAR double-targeting chimeric antigen receptor, the coding gene and the recombinant expression vector. The OCTS-CAR double-targeting chimeric antigen receptor includes a CD8 leader membrane receptor signal peptide, a double-antigen binding region, a CD8 Hinge chimeric receptor gemel, a CD8 transmembrane chimeric receptor transmembrane region, a CD28 chimeric receptor co-stimulatory factor, a CD134 chimeric receptor co-stimulatory factor and a TCR chimeric receptor T cell activating domain which are connected sequentially and in series, wherein the double-antigen binding region comprises heavy-chain VH and light-chain VL, connected in a certain mode, of two single-chain antibodies, an antibody Inner-Linker and an Inter-Linker between single-chain antibodies, and the two single-chain antibodies are formed by combining any two of a BCMA single-chain antibody, a CD319 single-chain antibody, a CD38 single-chain antibody, a PDL1 single-chain antibody and a CD123 single-chain antibody; in addition, the invention further provides a gene encoding the OCTS-CAR double-targeting chimeric antigen receptor, the recombinant expression vector and an establishment method and application of the gene encoding the OCTS-CAR double-targeting chimeric antigen receptor and the recombinant expression vector.

Description

technical field [0001] The invention belongs to the technical field of tumor immunotherapy, and specifically relates to a CAR dual-targeting chimeric antigen receptor based on OCTS technology, an encoding gene, an OCTS-CAR recombinant expression vector, and a construction method and application thereof for immunotherapy of malignant tumors . Background technique [0002] The theoretical basis of tumor immunotherapy is that the immune system has the ability to recognize tumor-associated antigens and regulate the body's ability to attack tumor cells (eg, highly specific cytolysis). In the 1950s, Burnet and Thomas proposed the theory of "immune surveillance", believing that the mutated tumor cells that often appear in the body can be recognized and eliminated by the immune system, which laid the theoretical foundation for tumor immunotherapy [Burnet FM. Immunological aspects of malignant disease . Lancet, 1967; 1: 1171-4]. Subsequently, various tumor immunotherapies, includin...

AI Technical Summary

Problems solved by technology

[0006] The disadvantage of option 1 is that it occupies the precious capacity of the lentiviral transgene vector, which is not conducive to loading other functional elements; the packaging efficiency of the transgene vector is low; the gene transduction efficiency is very low, and it is difficult to transduce into primary T lymphocytes

[0007] The disadvantage of Option 2 is that it needs two transductions, the overall efficiency of the two transductions is low, the transduction cycle time is long, and the primary cells are prone to aging, resulting in a decline in proliferation ability and a decline in the killing function, which affects the efficacy of tumor clearance

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