Chimeric antigen receptor T-cell therapy: design improvements and therapeutic strategies in cancer treatment

Objectives: To summarize important findings from research on chimeric antigen receptor (CAR) T-cell immunotherapy in cancer. We discuss CAR design, cell products, toxicity management, heterogenous solid tumors and allogeneic transfer. Methods: A review of literature was conducted. The available literature was selected on original research, state-of-the art design, relevance to the objective and journal impact factor. Results: First-generation CARs provide patient T cells with tumor-specific antigen recognition. Second- and third-generation CARs incorporate costimulatory domains for enhanced T-cell persistence and antitumor activity. Fourth-generation CAR T cells (TRUCKs) include a cytokine production cassette, and hold promise in the treatment of heterogenous solid tumors. Transduced cell phenotype and subset composition are important factors. Suicide genes and safety switches are designed to decrease potential toxicity. Multi-specific CAR T cells can address heterogenous tumors. Allogeneic, off-the-shelf CAR T cells might reduce the production delay. Conclusion: CAR T cells have revolutionized the immunotherapeutic treatment of cancer: exciting results in refractory and relapsed B-cell malignancies have been published. Neurologic complications, solid tumor management and allogeneic constructs require further research. In conclusion, further design adjustments will enable CAR T cells to decisively reshape the field of cancer immunotherapy.