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.
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.
Heukamp
L C
LC
Imperial Cancer Research Fund, Breast Cancer Biology Group, Guy's Hospital, London, United Kingdom.
van der Burg
S H
SH
Drijfhout
J W
JW
Melief
C J
CJ
Taylor-Papadimitriou
J
J
Offringa
R
R
D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D015234:HLA-A Antigens / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D020080:Tandem Repeat Sequences / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D018396:Mucin-1; D010446:Peptide Fragments