Pd1-specific chimeric antigen receptor as immunotherapy

Abstract

Provided herein are methods and compositions useful for treating PDL1 and / or PDL2 positive cancers through adoptive cell transfer of T cells genetically engineered to express a PD1-specific chimeric antigen receptor. Co-stimulatory domains such as Dap 10 may be included to enhance efficacy.

Description

technical field [0001] The present disclosure generally relates to chimeric antigen receptors targeting PDl ligands, and genetically engineered T cells expressing the receptors, for the treatment of cancer. In particular, chimeric antigen receptors may comprise co-stimulatory domains (eg Dap10) to enhance therapeutic efficacy. Background technique [0002] Engineering T cells with chimeric antigen receptors (CARs) is one approach to improve T cell efficacy against tumors. CARs are used to redirect T cell specificity and allow MHC-independent recognition of tumor-associated antigens, thereby enhancing tumor targeting. Advantages of using CAR-modified T cells for cancer therapy include the ability to recognize multiple tumor types, overcome mechanisms that tumors use to evade immune detection, and enhance T cell function. However, upregulation of inhibitory receptor expression on T cells and expression of inhibitory ligands in the tumor microenvironment limit CAR T cell resp...

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Problems solved by technology

However, upregulation of inhibitory receptor expression on T cells and expression of inhibitory ligands in the tumor microenvironment limit CAR T cell responses and efficacy

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