Identification of novel survivin-derived CTL epitopes.
The identification of tumor antigens, which are essential for the survival of tumor cells is a new avenue to prevent antigen loss variants emerging due to immunoselection, particularly during immune therapy. In the search for such immunogenic tumor antigens, we recently identified spontaneous cytotoxic lymphocyte (CTL) responses against the inhibitor of apoptosis protein survivin. Thus, we identified two HLA-A2-restricted, survivin-derived CTL epitopes, which both were targets for spontaneous CTL responses in melanoma, breast cancer, and CLL. Here, we extend these data and describe the characterization of novel HLA-A1-, HLA-A2-, HLA-A3-, and HLA-A11-restricted survivin epitopes on the basis of spontaneous CTL responses in cancer patients. These epitopes significantly increase the number of patients eligible for immunotherapy based on survivin derived peptides. Additionally, the collective targeting of several restriction elements is likely to decrease the risk of immune escape by HLA-allele loss.
Reker
Sine
S
Tumor Immunology Group, Division of Canter Biology, Danish Cancer Society, Copenhagen, Denmark.
Meier
Anders
A
Holten-Andersen
Lars
L
Svane
Inge Marie
IM
Becker
Jürgen C
JC
thor Straten
Per
P
Andersen
Mads Hald
MH
D000951:Antigens, Neoplasm / Q000276:immunology*; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015788:HLA-A1 Antigen / Q000276:immunology; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen / Q000276:immunology; D015791:HLA-A3 Antigen / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D008869:Microtubule-Associated Proteins / Q000276:immunology*; D009363:Neoplasm Proteins; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015788:HLA-A1 Antigen; D059870:HLA-A11 Antigen; D015789:HLA-A2 Antigen; D015791:HLA-A3 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D000077022:Survivin