Therapeutic potential of CRISPR/CAS9 genome modification in T cell-based immunotherapy of cancer

Abstract

Today, genome editing technologies like zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) are being used in clinical trials and the treatment of diseases like acquired immunodeficiency syndrome (AIDS) and cancer. CRISPR stands out as one of the most advanced tools for genome editing due to its simplicity and cost-effectiveness. It can selectively modify specific locations in the genome, offering new possibilities for treating human diseases. The CRISPR system uses ribonucleic acid-deoxyribonucleic acid (RNA-DNA) recognition to combat infections, regulate gene expression, and treat cancer. Chimeric antigen receptor (CAR) T-cell therapy, which uses T lymphocytes to eliminate cancer cells, can be improved by combining it with CRISPR technology. However, there are challenges in using CAR-T cells, including a lack of quantity and quality, exhaustion, neurotoxicity, cytokine release syndrome (CRS), B cell aplasia, tumor lysis syndrome, and anaphylaxis. Preclinical studies on CRISPR-edited CAR-T cells show promising results and targeting detrimental regulatory genes can enhance cancer treatment in the future.

Keywords: CAR-T cell therapy; CRISPR/Cas9; Immunotherapy for cancer.