Driving CAR-Based T-Cell Therapy to Success

作者：Jena Bipulendu; Moyes Judy S; Huls Helen; Cooper Laurence J N^*

来源：Current Hematologic Malignancy Reports, 2014, 9(1): 50-56.

DOI：10.1007/s11899-013-0197-7

• B-cell malignancies
• Chimeric antigen receptor
• Gene therapy
• T-cell therapy

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 focusses 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.

• 出版日期2014-3