Evolving CAR-T-Cell Therapy for Cancer Treatment: From Scientific Discovery to Cures

Simple Summary It is well recognized now that the development of drug resistance is one of the leading causes of treatment failure in conventional therapies. In comparison, recent improvements in immunotherapy showed promising results in eradicating cancer. Chimeric antigen receptor (CAR)-T-cell therapy is one of the cancer immunotherapies that uses patient's T cells and genetically modifies them to target cancer cells. Although CAR-T-cell therapy has shown remarkable success in treating blood cancer, it has proven far more limited in the treatment of solid tumors in different organs. This review article discussed the chronological development of CAR-T-cell therapies and their treatment options in different types of cancers. This article also addresses the current clinical challenges in CAR-T-cell therapy and recent advancements in developing novel therapeutic strategies with fewer side effects.Abstract In recent years, chimeric antigen receptor (CAR)-T-cell therapy has emerged as the most promising immunotherapy for cancer that typically uses patients' T cells and genetically engineered them to target cancer cells. Although recent improvements in CAR-T-cell therapy have shown remarkable success for treating hematological malignancies, the heterogeneity in tumor antigens and the immunosuppressive nature of the tumor microenvironment (TME) limits its efficacy in solid tumors. Despite the enormous efforts that have been made to make CAR-T-cell therapy more effective and have minimal side effects for treating hematological malignancies, more research needs to be conducted regarding its use in the clinic for treating various other types of cancer. The main concern for CAR-T-cell therapy is severe toxicities due to the cytokine release syndrome, whereas the other challenges are associated with complexity and immune-suppressing TME, tumor antigen heterogeneity, the difficulty of cell trafficking, CAR-T-cell exhaustion, and reduced cytotoxicity in the tumor site. This review discussed the latest discoveries in CAR-T-cell therapy strategies and combination therapies, as well as their effectiveness in different cancers. It also encompasses ongoing clinical trials; current challenges regarding the therapeutic use of CAR-T-cell therapy, especially for solid tumors; and evolving treatment strategies to improve the therapeutic application of CAR-T-cell therapy.