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Driving CAR-Based T-Cell Therapy to Success

  • Chronic Leukemias (S O'Brien, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

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 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.

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Conflict of Interest

Dr. Bipulendu Jena, Dr. Judy S Moyes, and Helen Huls each declare no potential conflicts of interest relevant to this article.

Dr. Laurence J. N. Cooper has been a consultant for American Stem Cells, Inc., GE Healthcare, Ferring Pharmaceuticals, Inc., and Bristol-Myers Squibb. Dr. Cooper has received multiple grants from foundations in the state of Texas and Federal to support research. Dr. Cooper received honoraria and payment for the development of education presentations including service on speakers’ bureaus from Miltenyi Biotec. Dr. Cooper received travel/accommodations expenses covered or reimbursed by Lonza.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Pediatrics (Unit #907), 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Bipulendu Jena, Judy S. Moyes, Helen Huls & Laurence J. N. Cooper

  2. The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA

    Laurence J. N. Cooper

  3. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Laurence J. N. Cooper

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  1. Bipulendu Jena
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  2. Judy S. Moyes
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  3. Helen Huls
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  4. Laurence J. N. Cooper
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Correspondence to Laurence J. N. Cooper.

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Jena, B., Moyes, J.S., Huls, H. et al. Driving CAR-Based T-Cell Therapy to Success. Curr Hematol Malig Rep 9, 50–56 (2014). https://doi.org/10.1007/s11899-013-0197-7

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  • DOI: https://doi.org/10.1007/s11899-013-0197-7

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