期刊
INTERNATIONAL JOURNAL OF CANCER
卷 125, 期 3, 页码 649-655出版社
WILEY
DOI: 10.1002/ijc.24414
关键词
tumor immunity; human; cytotoxic T cells; antigens/peptides/epitopes
类别
资金
- Research Council of Germany [SFB 456]
- DFG [BE 1579/4-1]
- Helmholtz Alliance
- European Union grant
The cancer-testis antigen NY-ESO-1 has been targeted as a tomor-associated antigen by immunotherapeutical strategies, such as cancer vaccines. The prerequisite for a T-cell-based therapy is the induction of T cells capable of recognizing the NY-ESO-1-expressing tumor cells. In this study, we generated human T lymphocytes directed against the immunodominant NY-ESO-1(157-165) epitope known to be naturally presented with HLA-A*0201. We succeeded to isolate autorestricted and allorestricted T lymphocytes with low, intermediate or high avidity TCRs against the NY-ESO-1 peptide. The avidity of the established CTL populations correlated with their capacity of lysing HLA-A2-positive, NYESO-1-expressing tumor cell lines derived from different origins, e.g. melanoma and myeloma. The allorestricted NY-ESO-1-specific T lymphocytes displayed TCRs with the highest avidity and best anti-tumor recognition activity. TCRs derived from allorestricted, NY-ESO-1-specific T cells may be useful reagents for redirecting primary T cells by TCR gene transfer and, therefore, may facilitate the development of adoptive transfer regimens based on TCR-transduced T cells for the treatment of NY-ESO-1-expressing hematological malignancies and solid tumors. (C) 2009 UICC
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