DNAM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma

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• 作者：Ming-Ru Wu ; Tong Zhang ; Andre Alcon ; Charles L. Sentman
• 关键词：CAR ; Gene therapy ; Immunotherapy ; Adoptive T cell therapy ; Melanoma
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：64
• 期：4
• 页码：409-418
• 全文大小：1,940 KB
• 参考文献：1. Porter, DL, Levine, BL, Kalos, M, Bagg, A, June, CH (2011) Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 365: pp. 725-733 CrossRef
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

Chimeric antigen receptor (CAR) T cell therapies hold great potential for treating cancers, and new CARs that can target multiple tumor types and have the potential to target non-hematological malignancies are needed. In this study, the tumor recognition ability of a natural killer cell-activating receptor, DNAM-1 was harnessed to design CARs that target multiple tumor types. DNAM-1 ligands, PVR and nectin-2, are expressed on primary human leukemia, myeloma, ovarian cancer, melanoma, neuroblastoma, and Ewing sarcoma. DNAM-1 CARs exhibit high tumor cell cytotoxicity but low IFN-γ secretion in vitro. In contrast to other CAR designs, co-stimulatory domains did not improve the expression and function of DNAM-1 CARs. A DNAM-1/CD3zeta CAR reduced tumor burden in a murine melanoma model in vivo. In conclusion, DNAM-1-based CARs may have the potential to treat PVR and nectin-2 expressing hematological and solid tumors.