PSCA (prostate stem cell antigen) and PD-L1 targeted CAR based on OCTS (one CAR with two ScFvs)-CAR (chimeric antigen receptor), encoding gene and expression vector

Abstract

The invention provides a PSCA (prostate stem cell antigen) and PD-L1 targeted CAR based on OCTS (one CAR with two ScFvs)-CAR (chimeric antigen receptor), an encoding gene, an OCTS-CAR-T recombinant expression vector as well as a construction method and an application of the OCTS-CAR-T recombinant expression vector. The PSCA and PD-L1 targeted CAR comprises a CD8 leader membrane receptor signal peptide, a double-antigen binding region, a CD8 Hinge chimeric receptor linker, a CD8 Transmembrane chimeric receptor transmembrane region, a CD28 chimeric receptor co-stimulator, an OX40 chimeric receptor co-stimulator and a TCR chimeric receptor T-cell activation domain which are connected in series sequentially, wherein the double-antigen binding region comprises heavy chains VH and light chains VL of PSCA and PDL1 single-chain antibodies, Inner-Linker in antibodies and Inter-Linker among the single-chain antibodies, which are in series connection or turn connection. Besides, the invention provides the encoding gene of the PSCA and PD-L1 targeted CAR, the recombinant expression vector as well as the construction method and the application of the recombinant expression vector.

Description

technical field [0001] The invention belongs to the technical field of tumor immunotherapy, and specifically relates to an OCTS-CAR-based anti-PSCA and PDL1 dual-targeting chimeric antigen receptor, encoding gene, recombinant expression vector and its construction method for malignant tumor immunotherapy and application. 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, including cytokine therapy, m...

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 Scheme 2 is that it requires 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 killing function, which affects the efficacy of tumor clearance

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