Boosting CAR-T cell therapy with CRISPR technology

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has made remarkable breakthroughs in treating cancers, especially hematologic malignancies, yet its broader application in cancer treatment is hindered by multiple challenges. Meanwhile, the development of clustered regularly interspaced short palindromic repeats (CRISPR) and its derived technologies has provided unprecedentedly efficient tools for genomic and cellular reprogramming, offering potential advantages for developing CAR-T cell therapy. There is hence a rapidly increasing interest in applying CRISPR to engineer CAR-T cells. Here, we present a review of recent research utilizing CRISPR to boost CAR-T cell therapy by enhancing its safety or effectiveness. We first provide an overview of CAR-T cell therapy and CRISPR technology, followed by discussions on how CRISPR and its related technologies can be adopted to tackle various issues associated with CAR-T cell therapy, either via knockout/knockin of specific genes or CRISPR-based screening. We also summarize clinical trials involving CRISPR-edited CAR-T cells. Lastly, we address the potential risks of applying CRISPR in CAR-T cell engineering.

Keywords

• chimeric antigen receptor (CAR)-T cell therapy
• clustered regularly interspaced short palindromic repeats (CRISPR)
• immunotherapy