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HLA‐B35‐restricted immune responses against survivin in cancer patients
Author(s) -
Reker Sine,
Becker Jürgen C.,
Svane Inge Marie,
Ralfkiaer Elisabeth,
Straten Per thor,
Andersen Mads Hald
Publication year - 2004
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/ijc.11634
Subject(s) - survivin , epitope , immunotherapy , immunology , immune system , melanoma , cytotoxic t cell , cancer , human leukocyte antigen , cancer research , antigen , cancer immunotherapy , medicine , biology , in vitro , biochemistry
Two HLA‐A2 restricted epitopes have recently been identified from the broadly expressed tumor antigen survivin, and several vaccination trials in cancer patients based on these survivin‐derived peptides have been initiated. Consequently, there is a crucial need for the identification of survivin epitopes restricted to other HLA‐molecules in order to extend the proportion of patients that can enter these ongoing clinical trials. In the present study, we characterized 2 survivin‐derived epitopes, which are restricted to HLA‐B35. Specific T‐cell reactivity against these survivin‐derived epitopes was found in the peripheral blood from patients with different B‐cell malignancies and melanoma. Substitution of the C‐terminal anchor residue of the survivin‐derived peptides improved the recognition by tumor‐infiltrating lymphocytes from melanoma patients. Furthermore, we demonstrated spontaneous cytotoxic T‐cell responses to survivin in a primary melanoma lesion. The characterization of these epitopes allows more patients can be included in the ongoing peptide‐based survivin vaccination trials against cancer. © 2003 Wiley‐Liss, Inc.