Driving CAR-based T-cell therapy to success
- PMID: 24488441
- PMCID: PMC3995024
- DOI: 10.1007/s11899-013-0197-7
Driving CAR-based T-cell therapy to success
Abstract
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.
Conflict of interest statement
Dr. Bipulendu Jena, Dr. Judy S Moyes, and Dr. Helen Huls each declare no potential conflicts of interest relevant to this article.
References
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Savoldo B, Ramos CA, Liu E, Mims MP, Keating MJ, Carrum G, et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011;121:1822–1826. •• Results published from this clinical trial showed that second generation CD19-28z CAR perform better in terms of in vivo expansion and persistence than first generation CD19z-CAR in a controlled repopulation experiment.
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