期刊
MOLECULAR THERAPY
卷 21, 期 5, 页码 1055-1063出版社
CELL PRESS
DOI: 10.1038/mt.2013.28
关键词
-
资金
- National Institutes of Health (NIH) [P50 CA086306]
- California Institute for Regenerative Medicine (CIRM) [RC1-00149-1]
- UCLA Center for AIDS Research NIH/National Institute of Allergy and Infectious Diseases [5P30 AI028697]
- UCLA AIDS Institute
- NATIONAL CANCER INSTITUTE [P50CA086306, P01CA132681] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P30AI028697] Funding Source: NIH RePORTER
Current tumor immunotherapy approaches include the genetic modification of peripheral T cells to express tumor antigen-specific T-cell receptors (TCRs). The approach, tested in melanoma, has led to some limited success of tumor regression in patients. Yet, the introduction of exogenous TCRs into mature T cells entails an underlying risk; the generation of autoreactive clones due to potential TCR mispairing, and the lack of effective negative selection, as these peripheral cells do not undergo thymic selection following introduction of the exogenous TCR. We have successfully generated MART-1-specific CD8 T cells from genetically modified human hematopoietic stem cells (hHSC) in a humanized mouse model. The advantages of this approach include a long-term source of antigen specific T cells and proper T-cell selection due to thymopoiesis following expression of the TCR. In this report, we examine the molecular processes occurring on endogenous TCR expression and demonstrate that this approach results in exclusive cell surface expression of the newly introduced TCR, and the exclusion of endogenous TCR cell surface expression. This suggests that this stem cell based approach can provide a potentially safer approach for anticancer immunotherapy due to the involvement of thymic selection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据