Smart CARs engineered for cancer immunotherapy.
OBJECTIVE
Chimeric antigen receptors (CARs) are synthetic immunoreceptors, which can redirect T cells to selectively kill tumor cells, and as 'living drugs' have the potential to generate long-term antitumor immunity. Given their recent clinical successes for the treatment of refractory B-cell malignancies, there is a strong push toward advancing this immunotherapy to other hematological diseases and solid cancers. Here, we summarize the current state of the field, highlighting key variables for the optimal application of CAR T cells for cancer immunotherapy.


RESULTS
Advances in CAR T-cell therapy have highlighted intrinsic CAR design and T-cell manufacturing methods as critical components for maximal therapeutic success. Similarly, addressing the unique extrinsic challenges of each tumor type, including overcoming the immunosuppressive tumor microenvironment and tumor heterogeneity, and mitigating potential toxicity, will dominate the next wave of CAR T-cell development.


CONCLUSIONS
CAR T-cell therapeutic optimization, including intrinsic and extrinsic factors, is critical to developing effective CAR T-cell therapies for cancer. The excitement of CAR T-cell immunotherapy has just begun, and will continue with new insights revealed in laboratory research and in ongoing clinical investigations.
Departments of Cancer Immunotherapy and Tumor Immunology Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute at City of Hope National Medical Center, Duarte, California, USA.
Saul J
SJ
Priceman
Stephen J
SJ
Forman
Christine E
CE
Brown
D002454:Cell Differentiation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology*; D059016:Tumor Microenvironment / Q000276:immunology
D011948:Receptors, Antigen, T-Cell