The Human T-Box Mesodermal Transcription Factor Brachyury Is a Candidate Target for T-Cell–Mediated Cancer Immunotherapy
Purpose: Identification of tumor antigens is essential in advancing immune-based therapeutic interventions in cancer. Particularly attractive targets are those molecules that are selectively expressed by malignant cells and that are also essential for tumor progression. Experimental Design and Resul...
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Veröffentlicht in: | Clinical cancer research 2007-04, Vol.13 (8), p.2471-2478 |
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Zusammenfassung: | Purpose: Identification of tumor antigens is essential in advancing immune-based therapeutic interventions in cancer. Particularly
attractive targets are those molecules that are selectively expressed by malignant cells and that are also essential for tumor
progression.
Experimental Design and Results: We have used a computer-based differential display analysis tool for mining of expressed sequence tag clusters in the human
Unigene database and identified Brachyury as a novel tumor antigen. Brachyury, a member of the T-box transcription factor
family, is a key player in mesoderm specification during embryonic development. Moreover, transcription factors that control
mesoderm have been implicated in the epithelial-mesenchymal transition (EMT), which has been postulated to be a key step during
tumor progression to metastasis. Reverse transcription-PCR analysis validated the in silico predictions and showed Brachyury expression in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testis, as well as in cell lines
derived from lung, colon, and prostate carcinomas, but not in the vast majority of the normal tissues tested. An HLA-A0201
epitope of human Brachyury was identified that was able to expand T lymphocytes from blood of cancer patients and normal donors
with the ability to lyse Brachyury-expressing tumor cells.
Conclusions: To our knowledge, this is the first demonstration that ( a ) a T-box transcription factor and ( b ) a molecule implicated in mesodermal development, i.e., EMT, can be a potential target for human T-cell–mediated cancer immunotherapy. |
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ISSN: | 1078-0432 1557-3265 |
DOI: | 10.1158/1078-0432.CCR-06-2353 |