Driving CAR-based T-cell therapy to success.
T cells that have been genetically modified, activated, and propagated ex vivo can be infused to control tumor progression in patients who are refractory to conventional treatments. Early-phase clinical trials demonstrate that the tumor-associated antigen (TAA) CD19 can be therapeutically engaged through the enforced expression of a chimeric antigen receptor (CAR) on clinical-grade T cells. Advances in vector design, the architecture of the CAR molecule especially as associated with T-cell co-stimulatory pathways, and understanding of the tumor microenvironment, play significant roles in the successful treatment of medically fragile patients. However, some recipients of CAR(+) T cells demonstrate incomplete responses. Understanding the potential for treatment failure provides a pathway to improve the potency of adoptive transfer of CAR(+) T cells. High throughput single-cell analyses to understand the complexity of the inoculum coupled with animal models may provide insight into the therapeutic potential of genetically modified T cells. This review focuses on recent advances regarding the human application of CD19-specific CAR(+) T cells and explores how their success for hematologic cancers can provide a framework for investigational treatment of solid tumor malignancies.
Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Pediatrics (Unit #907), 1515 Holcombe Blvd., Houston, TX, 77030, USA.
Bipulendu
B
Jena
Judy S
JS
Moyes
Helen
H
Huls
Laurence J N
LJ
Cooper
D018941:Antigens, CD19 / Q000276:immunology; D002986:Clinical Trials as Topic; D005818:Genetic Engineering; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018941:Antigens, CD19; D011948:Receptors, Antigen, T-Cell