CRISPR–Cas9 applications in T cells and adoptive T cell therapies

• Published in: Cellular & molecular biology letters Vol. 29; no. 1; pp. 52 - 25
• Main Authors: Chen, Xiaoying, Zhong, Shuhan, Zhan, Yonghao, Zhang, Xuepei
• Format: Journal Article
• Language: English
• Published: England BioMed Central 12.04.2024; BMC
• Subjects: Adoptive T cell therapy; Antigens; Autoimmune diseases; Cancer; CAR-T; Cell activation; Cell Differentiation; Cell growth; Cell therapy; Clinical trials; CRISPR; CRISPR-Cas Systems - genetics; CRISPR–Cas9; Cytokines; Genes; Genome editing; Genomes; Homeostasis; Humans; Immune checkpoint inhibitors; Immune system; Infections; Inflammation; Inflammatory diseases; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Medical prognosis; Metabolism; Microenvironments; Proteins; Systems stability; T cell receptors; T cells; T-Lymphocytes; TCR-T; TIL; Transcription factors; Tumor necrosis factor-TNF; Tumors; T cells; CAR-T; TCR-T; CRISPR–Cas9; Adoptive T cell therapy; TIL
• ISSN: 1689-1392; 1425-8153; 1689-1392
• DOI: 10.1186/s11658-024-00561-1

T cell immunity is central to contemporary cancer and autoimmune therapies, encompassing immune checkpoint blockade and adoptive T cell therapies. Their diverse characteristics can be reprogrammed by different immune challenges dependent on antigen stimulation levels, metabolic conditions, and the degree of inflammation. T cell-based therapeutic strategies are gaining widespread adoption in oncology and treating inflammatory conditions. Emerging researches reveal that clustered regularly interspaced palindromic repeats–associated protein 9 (CRISPR–Cas9) genome editing has enabled T cells to be more adaptable to specific microenvironments, opening the door to advanced T cell therapies in preclinical and clinical trials. CRISPR–Cas9 can edit both primary T cells and engineered T cells, including CAR-T and TCR-T, in vivo and in vitro to regulate T cell differentiation and activation states. This review first provides a comprehensive summary of the role of CRISPR–Cas9 in T cells and its applications in preclinical and clinical studies for T cell-based therapies. We also explore the application of CRISPR screen high-throughput technology in editing T cells and anticipate the current limitations of CRISPR–Cas9, including off-target effects and delivery challenges, and envisioned improvements in related technologies for disease screening, diagnosis, and treatment.