Cancer Immunity 3:18 (2003)

Identification of an HLA-A*02 restricted immunogenic peptide derived from the cancer testis antigen HOM-MEL-40/SSX2

Claudia Wagner¹, Frank Neumann¹, Boris Kubuschok¹, Evi Regitz¹, Axel Mischo¹, Stefan Stevanovic², Michael Friedrich³, Werner Schmidt³, Hans-Georg Rammensee², and Michael Pfreundschuh¹

¹Med. Klinik I, Saarland University Medical School, D-66424 Homburg, Germany
²Institute for Cell Biology, Department of Immunology, Eberhard-Karls-Universität, D-72074 Tübingen, Germany
³Universitäts-Frauenklinik, Saarland University Medical School, D-66424 Homburg, Germany

Keywords: human, breast cancer, T lymphocyte epitopes, SSX2, HLA-A2

Abstract

HOM-MEL-40/SSX2 is a SEREX-defined cancer testis antigen with frequent expression in various human neoplasms. To search for HLA-A*0201 restricted peptides that induce HOM-MEL-40/SSX2-specific CD8+ responses in breast cancer patients, we used the SYFPEITHI algorithm to identify three HOM-MEL-40/SSX2-derived nonamers with high binding affinity for HLA-A*0201, which has a prevalence of 40% in the Caucasian population. Of the three peptides, p41-49 and p103-111 but not p167-175 had been shown to be processed by the proteasome. Only stimulation with p103-111 induced HOM-MEL-40-specific CTLs in 5/7 patients with HOM-MEL-40/SSX2 positive breast cancers and in 6/11 healthy controls. HLA-A*0201 restriction of p103-111 was demonstrated by blocking with specific antibodies. The natural processing and presentation of p103-111 was demonstrated by the recognition of the HOM-MEL-40/SSX2 positive cell line SK-MEL-37 and of COS7/A2 cells transfected with HOM-MEL-40/SSX2 by p103-111 specific CD8+ cells. No correlation was found between CD8+ T-cell responses against p103-111 and anti-HOM-MEL-40/SSX2 antibody titers in the serum of patients, suggesting that CD8+ and B-cell responses against HOM-MEL-40/SSX2 are regulated independently. p103-111 holds promise as a broadly applicable peptide vaccine for patients with HOM-MEL-40/SSX2 positive neoplasms.