PD1-targeted chimeric antigen receptor-modified regulatory T cells, method for producing same and use thereof

Abstract

We provide PD1-targeted chimeric antigen receptor-modified regulatory T cells, as well as methods for their production and use. To address the current challenges of peripheral blood Treg cell isolation, purification, and expansion, as well as their antigen nonspecificity, we target PD1 on the T cell surface and engineer the extracellular domain of the CAR molecule to be a single-chain antibody constructed with a PD1 ligand, i.e., the extracellular domain of PD-L1, or an agonist antibody targeting PD1. Furthermore, co-expression of the FOXP3 transcription factor and the CAR fusion protein directly induces intracellular autodifferentiation from peripheral blood T cells into CAR-Tregs, thereby addressing the low abundance of peripheral blood-derived Tregs. By generating intracellularly induced, antigen-specific CAR-Tregs, we can suppress the proliferation and cytotoxicity of effector T cells, thereby achieving the goals of ameliorating aGVHD and controlling autoimmune diseases.

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