Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients.
During the last decade, a large number of human tumor-associated antigens have been identified that are recognized by CTLs in a MHC-restricted fashion. The apoptosis inhibitor protein survivin is overexpressed in most human cancers, and inhibition of its function results in increased apoptosis. Therefore, this protein may serve as a target for therapeutic CTL responses. Here, using CTL epitopes deduced from survivin, we describe specific T-cell reactivity against this antigen in peripheral blood from chronic lymphatic leukemia patients and in tumor-infiltrated lymph nodes from melanoma patients by ELISPOT analysis. CTL responses against two survivin-deduced peptide epitopes were detected in three of six melanoma patients and three of four chronic lymphatic leukemia patients. No T-cell reactivity was detected in peripheral blood lymphocytes from six healthy controls. Thus, survivin may serve as an important and widely applicable target for anticancer immunotherapeutic strategies.
Andersen
M H
MH
Department of Tumor Cell Biology, Danish Cancer Society, Copenhagen. mha@cancer.dk
Pedersen
L O
LO
Becker
J C
JC
Straten
P T
PT
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008545:Melanoma / Q000097:blood / Q000276:immunology*; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011506:Proteins / Q000276:immunology* / Q000378:metabolism; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D000951:Antigens, Neoplasm; C107489:BIRC5 protein, human; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D011506:Proteins; D000077022:Survivin