Screening for Gene Modifications to Improve T Cell Function

A major barrier in CAR-T cell therapies has been T cell exhaustion, which affects the durability and effectiveness of treatments, particularly for solid tumors. This is caused by chronic tumoral T cell activation which limits their ability to kill the cancer cells due to impaired proliferation, cytotoxicity, and effector functions. Therefore, identifying methods to improve T cell function and resist exhaustion via genetic engineering of T cells represents a highly promising therapeutic approach and major focus of the cell therapy field.

Stanford researchers have developed an in vitro T cell exhaustion model with genome-wide CRISPR screens for genes that improve these T cell functions. Several of these genes have been identified that not only prevent exhaustion but also improve T cell survival in the presence of chronic antigen in vitro and persistence in tumor models in vivo. Modification of these genes can improve therapeutics in the CAR-T setting as well as other adoptive T cell-based therapies.

Stage of Development
Proof of concept with in vitro and in vivo data