HLA-B35-restricted immune responses against survivin in cancer patients.
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.
Reker
Sine
S
Tumor Immunology Group, Division of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
Becker
Jürgen C
JC
Svane
Inge Marie
IM
Ralfkiaer
Elisabeth
E
Straten
Per-thor
PT
Andersen
Mads Hald
MH
D000483:Alleles; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism; D000939:Epitopes; D005805:Genes, MHC Class I; D015797:HLA-B35 Antigen / Q000096:biosynthesis*; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007167:Immunotherapy; D051034:Inhibitor of Apoptosis Proteins; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D008545:Melanoma / Q000628:therapy; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000276:immunology*; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D000939:Epitopes; D015797:HLA-B35 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D000077022:Survivin