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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
Author(s) -
Heukamp Lukas C.,
van der Burg Sjoerd H.,
Drijfhout JanWouter,
Melief Cornelis J.M.,
TaylorPapadimitriou Joyce,
Offringa Rienk
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1051>3.0.co;2-z
Subject(s) - muc1 , epitope , biology , ctl* , cytotoxic t cell , microbiology and biotechnology , immunology , antigen , cd8 , in vitro , genetics
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/K b transgenic mice, 3 peptides, namely MUC 79–87 (TLAPATEPA), MUC 167–175 (ALGSTAPPV) and MUC 264–272 (FLSFHISNL) elicit peptide‐specific cytotoxic T lymphocyte (CTL) immunity, which protects these mice against a challenge with MUC1, A2/K b ‐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.