期刊
ONCOGENE
卷 37, 期 27, 页码 3686-3697出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41388-018-0187-2
关键词
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资金
- Cancer Center Core Grant [CA16672]
- RO1 [CA124782, CA120956, CA141303]
- P01 [CA148600]
- SPORES [CA100632, CA136411, CA00632]
- Albert J Ward Foundation
- Alex's Lemonade Stand Foundation
- Burroughs Wellcome Fund
- Cancer Prevention and Research Institute of Texas
- Charles B. Goddard Foundation of Texas
- CLL Global Research Foundation
- Energy Transfer Partners
- Estate of Noelan L. Bibler
- Gillson Longenbaugh Foundation
- Harry T. Mangurian, Jr., Fund for Leukemia Immunotherapy
- Khalifa Bin Zayed Al Nahyan Foundation
- Kleberg Foundation
- Leukemia and Lymphoma Society
- Lung Cancer Research Foundation
- Lung Cancer Moon Shot
- Lymphoma Research Foundation
- Miller Foundation
- National Foundation for Cancer Research
- NIH Cancer Center Support Grant Pediatric Cancer Research Foundation [CA016672]
- Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy
- University of Texas MD Anderson Cancer Center Sister Institution Network Fund
- University of Texas Moon Shot Fund
- University of Texas Southwestern Medical Center [5 P50 CA070907]
- University of Texas MD Anderson Cancer Center NIH Lung SPORE Grant [5 P50 CA070907]
- William Lawrence and Blanche Hughes Children's Foundation
The CD56 antigen (NCAM-1) is highly expressed on several malignancies with neuronal or neuroendocrine differentiation, including small-cell lung cancer and neuroblastoma, tumor types for which new therapeutic options are needed. We hypothesized that CD56-specific chimeric antigen receptor (CAR) T cells could target and eliminate CD56-positive malignancies. Sleeping Beauty transposon-generated CD56R-CAR T cells exhibited a beta T-cell receptors, released antitumor cytokines upon co-culture with CD56(+) tumor targets, demonstrated a lack of fratricide, and expression of cytolytic function in the presence of CD56(+) stimulation. The CD56R-CAR(+) T cells are capable of killing CD56(+) neuroblastoma, glioma, and SCLC tumor cells in in vitro co-cultures and when tested against CD56(+) human xenograft neuroblastoma models and SCLC models, CD56R-CAR(+) T cells were able to inhibit tumor growth in vivo. These results indicate that CD56-CARs merit further investigation as a potential treatment for CD56(+) malignancies.
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