CRISPR-edited CAR-T cells: Using CRISPR-Cas9 to Improve CAR-T Therapy

Abstract

One of the cornerstones of cancer immunotherapy, chimeric antigen receptor T cell (CAR-T) immunotherapy is a treatment comprising of T cells transfected with artificial receptors that target a specific tumor antigen, potentiating tumor destruction. Despite the effectiveness of this technique in treating hematopoietic malignancies, efficacy against other cancers leaves much to be desired. CAR-T therapy's anti-tumor effectiveness, safety, and accessibility are hampered by issues such T cell exhaustion, toxicity, and ineffective production techniques. With the advent of CRISPR-Cas9 technology, allowing ease of genome editing, it is now possible to address these challenges. By introducing a double-strand break at a particular genomic location, this gene editing technology can be utilized to target inhibitors of T lymphocyte function, directed to specific loci to produce a less toxic product, and engineer allogeneic CAR-T cells. However, CRISPR-Cas9 confers its own limitations, including off-target editing. This review introduces the applications of CRISPR technology to CAR-T therapy and evaluates how the technology can optimize the effectiveness, safety, and product availability of this cancer immunotherapy. This paper also addresses some of the potential drawbacks of CRISPR-edited CAR-T cells.