Journal
HUMAN GENE THERAPY
Volume 23, Issue 5, Pages 444-450Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/hum.2011.167
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Funding
- Cancer Center [CA16672]
- RO1 [CA124782, CA120956, CA141303]
- R33 [CA116127]
- Burroughs Wellcome Fund
- Cancer Prevention Research Institute of Texas
- DOD
- Gillson Longenbaugh Foundation
- Harry T. Mangurian, Jr., Foundation
- Institute of Personalized Cancer Therapy
- Leukemia and Lymphoma Society
- Lymphoma Research Foundation
- Miller Foundation
- Mr. and Mrs. Joe H. Scales
- National Foundation for Cancer Research
- Pediatric Cancer Research Foundation
- William Lawrence and Blanche Hughes Children's Foundation
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Limited curative treatment options exist for patients with advanced B-lymphoid malignancies, and new therapeutic approaches are needed to augment the efficacy of hematopoietic stem-cell transplantation (HSCT). Cellular therapies, such as adoptive transfer of T cells that are being evaluated to target malignant disease, use mechanisms independent of chemo-and radiotherapy with nonoverlapping toxicities. Gene therapy is employed to generate tumor-specific T cells, as specificity can be redirected through enforced expression of a chimeric antigen receptor (CAR) to achieve antigen recognition based on the specificity of a monoclonal antibody. By combining cell and gene therapies, we have opened a new Phase I protocol at the MD Anderson Cancer Center (Houston, TX) to examine the safety and feasibility of administering autologous genetically modified T cells expressing a CD19-specific CAR (capable of signaling through chimeric CD28 and CD3-zeta) into patients with high-risk B-lymphoid malignancies undergoing autologous HSCT. The T cells are genetically modified by nonviral gene transfer of the Sleeping Beauty system and CAR(+) T cells selectively propagated in a CAR-dependent manner on designer artificial antigen-presenting cells. The results of this study will lay the foundation for future protocols including CAR(+) T-cell infusions derived from allogeneic sources.
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