Identification of three non-VNTR MUC1-derived HLA-A*0201-restricted T-cell epitopes that induce protective anti-tumor immunity in HLA-A2/K^b-transgenic mice

Autor:	Heukamp, Lukas C., Burg, Sjoerd H. van der, Drijfhout, Jan-Wouter, Melief, Cornelis J.M., Taylor-Papadimitriou, Joyce, Offringa, Rienk
Zdroj:	International Journal of Cancer; 1 February 2001, Vol. 91 Issue: 3 p385-392, 8p
Abstrakt:	The human epithelial mucin MUC1 is over-expressed in more than 90% of carcinomas of the breast, ovary, and pancreas as well as in some other tumours, making it a potential target for tumour immunotherapy. We have identified several MUC1-derived peptides mapping outside the variable number tandem repeat region that comply with the peptide-binding motif for HLA-A*0201 and that become processed into stable major histocompatibility complex-peptide complexes as assessed by in vitro assays. In A2/Kb transgenic mice, 3 peptides, namely MUC79–87 (TLAPATEPA), MUC167–175 (ALGSTAPPV) and MUC264–272 (FLSFHISNL) elicit peptide-specific cytotoxic T lymphocyte (CTL) immunity, which protects these mice against a challenge with MUC1, A2/Kb-expressing tumour cells. These peptides therefore represent naturally processed MUC1-derived CTL epitopes that could be used as components in peptide-based vaccines and for the analysis of anti-MUC1 CTL responses in A*0201-positive patients with MUC1-expressing tumours. © 2001 Wiley-Liss, Inc.
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