Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antigens, Neoplasm / immunology
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Enzyme-Linked Immunosorbent Assay
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Epitopes, T-Lymphocyte / immunology
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HLA-A2 Antigen / immunology
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HLA-A2 Antigen / metabolism
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Humans
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Inhibitor of Apoptosis Proteins
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Leukemia, Lymphocytic, Chronic, B-Cell / blood
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Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
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Lymph Nodes / immunology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Melanoma / blood
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Melanoma / immunology*
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Microtubule-Associated Proteins*
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Neoplasm Proteins
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Protein Binding
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Proteins / immunology*
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Proteins / metabolism
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Survivin
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology*
Substances
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Antigens, Neoplasm
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BIRC5 protein, human
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Epitopes, T-Lymphocyte
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HLA-A2 Antigen
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Inhibitor of Apoptosis Proteins
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Microtubule-Associated Proteins
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Neoplasm Proteins
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Peptide Fragments
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Proteins
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Survivin