Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients

Cancer Res. 2001 Feb 1;61(3):869-72.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte / immunology
  • HLA-A2 Antigen / immunology
  • HLA-A2 Antigen / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Leukemia, Lymphocytic, Chronic, B-Cell / blood
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Lymph Nodes / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Melanoma / blood
  • Melanoma / immunology*
  • Microtubule-Associated Proteins*
  • Neoplasm Proteins
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Protein Binding
  • Proteins / immunology*
  • Proteins / metabolism
  • Survivin
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antigens, Neoplasm
  • BIRC5 protein, human
  • Epitopes, T-Lymphocyte
  • HLA-A2 Antigen
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Peptide Fragments
  • Proteins
  • Survivin