octs-car dual targeting chimeric antigen receptor, coding gene, recombinant expression vector and its construction and application

Abstract

Provided in the present invention are an OCTS-CAR dual targeting chimeric antigen receptor based on OCTS technology, an encoding gene, an OCTS-CAR-T recombinant expression vector and a construction method and the use thereof. The OCTS-CAR dual targeting chimeric antigen receptor comprises a CD8 leader membrane receptor signal peptide, a dual antigen binding region, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane region, a CD28 chimeric receptor costimulatory factor, a CD134 chimeric receptor costimulatory factor and a TCR chimeric receptor T cell activation domain sequentially connected in series, wherein the dual antigen binding region comprises a heavy chain VH and a light chain VL of the two single chain antibodies connected in a certain manner, the hinge Inner-Linker within the antibody and the hinge Inter-Linker between the single chain antibodies, and the two single chain antibodies refer to the combination of any two of the BCMA single chain antibody, CD319 single chain antibody, CD38 single chain antibody, PDL1 single chain antibody and CD123 single chain antibody. In addition, also provided are the gene encoding the OCTS-CAR dual targeting chimeric antigen receptor, the recombinant expression vector and the construction method and use thereof.

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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