Dual CAR (chimeric antigen receptor) structure targeting bispecific sites and application thereof

Abstract

The invention belongs to the technical field of immunotherapy, and particularly relates to a dual-CAR (chimeric antigen receptor) structure targeting bispecific sites, an expression vector containing the dual-CAR structure of the bispecific sites, an immune cell and an application. The dual-CAR structure is a ScFv1-hinge-transmembrane-41BB intracellular signal-CD3 [zeta]-self-cleavage polypeptide-ScFv2-hinge-transmembrane-CD28 intracellular signal-CD3 [zeta] or a ScFv1-hinge- transmembrane-CD28 intracellular signal-CD3 [zeta]-self-cleavage polypeptide-ScFv2-hinge-transmembrane-41BB intracellular signal-CD3 [zeta]. The construction of the dual-CAR structure overcomes the technical effect defect of dual-target CAR in the prior art, two different tumor antigens can be targeted at the same time, the killing rate of the tumor cells is increased, and the probability of immune escape of the tumor cells is reduced.

Description

technical field [0001] The invention belongs to the technical field of immunotherapy, and specifically relates to a dual CAR structure targeting a bispecific site, and an expression vector, immune cells and applications of the dual CAR structure containing the dual specific site. Background technique [0002] CAR-T (Chimeric Antigen Receptor T) cell therapy has achieved remarkable results in the treatment of hematological malignancies. However, due to the heterogeneity of tumors, especially solid tumors, more than one target antigen is often expressed on the surface of tumor cells, and with the progress of research, researchers have also found that a small number of patients treated with CAR-T cells have down-regulated or mutated tumor cells. The expressed CAR-T target antigen escapes (Robbie G. Majzner et al. (2018) Tumor AntigenEscape from CAR T-cell Therapy), resulting in poor therapeutic effect and recurrence. Therefore, it is necessary to design a CAR structure targeti...

AI Technical Summary

Problems solved by technology

However, due to the heterogeneity of tumors, especially solid tumors, more than one target antigen is often expressed on the surface of tumor cells, and with the progress of research, researchers have also found that a small number of patients treated with CAR-T cells have down-regulated or mutated tumor cells. The expressed CAR-T target antigen escapes (Robbie G.Majzner et al. (2018) Tumor AntigenEscape from CAR T-cell Therapy), resulting in poor therapeutic effect and recurrence

Therefore, it is necessary to design a CAR structure targeting multiple targets. Simply expressing two CARs with different targets at the same time involves different CAR structures with different infectivity, and will generate a variety of CAR-T cell subsets, which is not conducive to the clinical application of the product. ; If only two simple CAR structures with different targets are connected in series in one carrier, such a large CAR carrier is not easy to transduce T cells. Different structures involve different CAR carrier virus preparation capabilities and different CAR transduction capabilities. There are many factors such as different stimuli and different curative effects

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