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Comparative study on the immunogenicity between an HLA-A24-restricted cytotoxic T-cell epitope derived from survivin and that from its splice variant survivin-2B in oral cancer patients

Jun-ichi Kobayashi1,2 email, Toshihiko Torigoe1 email, Yoshihiko Hirohashi1 email, Satomi Idenoue3 email, Akihiro Miyazaki2 email, Akira Yamaguchi2 email, Hiroyoshi Hiratsuka2 email and Noriyuki Sato1 email

Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

Department of Oral Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan

Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan

author email corresponding author email

Journal of Translational Medicine 2009, 7:1doi:10.1186/1479-5876-7-1

Published: 6 January 2009

Abstract

Background

We previously reported an HLA-A24-restricted cytotoxic T-cell epitope, Survivin-2B80-88, derived from a splice variant of survivin, survivin-2B. In this report, we show a novel HLA-A24-restricted T-cell epitope, Survivin-C58, derived from a wild type survivin, and compared their immunogenicity in oral cancer patients.

Methods

By stimulating peripheral blood lymphocytes of HLA-A24-positive cancer patients with Survivin-C58 peptide in vitro, the peptide-specific CTLs were induced. In order to compare the immunogenic potential between C58 peptide and 2B80-88 peptide, peripheral blood T-cells from thirteen HLA-A24-positive oral cancer patients were stimulated with either or both of these two peptides.

Results

Survivin-2B80-88 peptide-specific CTLs were induced from four patients, and C58 peptide-specific CTLs were induced from three out of eight patients with over stage II progression. The CTLs exerted cytotoxicity against HLA-A24-positive tumor cells. In contrast, CTL induction failed from a healthy volunteer and all four patients with cancer stage I.

Conclusion

It was indicated that a splicing variant-derived peptide and wild type survivin-derived peptide might have a comparable potency of CTL induction, and survivin targeting immunotherapy using survivin-2B80-88 and C58 peptide cocktail should be suitable for HLA-A24+ oral cancer patients.


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