Cell culturing method for improving curative effect and lasting effect performance of chimeric antigen receptor T cells

Abstract

The invention provides a cell culturing method for improving the curative effect and lasting effect performance of chimeric antigen receptor T cells. By adding a tyrosine kinase inhibitor dasatinib (dasatinib), activation signal transmission of the CAR-T cells is reduced, the terminal differentiation of the CAR-T cells is inhibited, the proportion of naive T cells and central memory T cells in a CAR-T cell product is increased, and the depletion trend of the CAR-T cells is inhibited. The method solves the problems of the terminal differentiation and depletion trend of the CAR-T cells in the in-vitro culture process. The method is simple in culture process, easy to implement, low in cost and safe and reliable in clinic application; the proportion of the naive T cells and the central memoryT cells of the cultured CAR-T cells is high, the depletion trend of the CAR-T cells is avoided, and the good repeatability is achieved; the cultured CAR-T cells show the better curative effect and thebetter in-vivo lasting effect performance and have high application and popularization value.

Description

technical field [0001] The invention belongs to the field of immunology and cell therapy research, and relates to a cell culture method for improving the curative effect and persistence of chimeric antigen receptor T cells. Central memory T cells, a culture method that reduces exhaustion of CAR-T cells. Background technique [0002] Chimeric antigen receptor modified T (chimeric antigen receptor modified T, CAR-T) cell immunotherapy has become the most promising treatment method in immune targeted therapy in recent years. Its working principle is to use genetic engineering technology to recognize a certain The antigen-binding part of the specific single-chain monoclonal antibody of a tumor antigen, the tyrosine activation motif of the T cell receptor and the co-stimulatory molecule are coupled into a chimeric protein in vitro, and T cells are transfected by viral vectors and other methods , so that T cells can specifically recognize tumor cells and transmit signals into the...

AI Technical Summary

Problems solved by technology

Naive T cells and central memory T cells in CAR-T cell preparations show long-term survival in vivo, while CAR-T cells differentiated to terminal stages such as effector memory and effectors cannot last in vivo; at the same time, depletion of CAR-T T cells continuously express high levels of inhibitory receptors such as PD1, TIM3, and LAG3, have low proliferation ability, low cytokine release ability, and are prone to apoptosis, which severely limits the persistent effector function of CAR-T in vivo

However, there is currently no method to solve the terminal differentiation and exhaustion tendency of CAR-T cells during in vitro culture.

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