Challenges and future perspectives for high-throughput chimeric antigen receptor T cell discovery

Abstract

Novel chimeric antigen receptor (CAR) T cell designs are being developed to overcome challenges with tumor recognition, trafficking, on-target but off-tumor binding, cytotoxicity, persistence, and immune suppression within the tumor microenvironment. Whereas traditional CAR engineering is an iterative, hypothesis-driven process in which novel designs are rationally constructed and tested for in vivo efficacy, drawing from the fields of small-molecule and protein-based therapeutic discovery, we consider how high-throughput, functional screening technologies are beginning to be applied for the development of promising CAR candidates. We review how the development of high-throughput screening methods has the potential to streamline the CAR discovery process, ultimately improving efficiency and clinical efficacy.