Immune Reprogramming

"Recent innovations in CRISPR-based technologies are rapidly advancing toward the clinic, offering tools to correct genetic defects, reprogram immune cells, and remodel the TME (see Tumor Microenvironment) directly in patients. Across solid tumors and blood cancers, these technologies are being explored not only to enhance existing therapeutic strategies, such as immunotherapies and adoptive cell therapies, but also as a treatment itself.\n\nIn several recent studies, CRISPR-based systems have been used to improve the effectiveness of established treatments by activating the immune system. For example, researchers have enhanced the efficacy of adoptive T-cell therapies (see Sidebar 41) by increasing how long T cells can be active and how quickly they remove cancer cells in both blood cancer and solid tumors (1071)Patel RP, et al. (2024) Sci Immunol, 9: eadn6509.. In addition, researchers have genetically engineered natural killer (NK) cells to resist immunosuppressive signals in the TME and improve clinical performance of immunotherapy (1072)Rea A, et al. (2025) Nat Immunol, 26: 582.. Tumor-infiltrating lymphocytes (TILs) modified with CRISPR to block proteins that weaken the immune system are also showing early promise in clinical trials (1073)Lou E, et al. (2025) Lancet Oncol, 26: 559.. These advances contribute to a growing trend of using CRISPR to reprogram immune cells for greater antitumor potency (1074)Feng X, et al. (2024) Exp Hematol Oncol, 13: 102.(1075)Tarannum M, et al. (2025) Nat Biotechnol, 43: 516.(1076)Khoshandam M, et al. (2024) Genes Dis, 11: 101121.."