Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA-A*0201-restricted epitopes

Int J Cancer. 2004 Mar 1;108(6):863-70. doi: 10.1002/ijc.11653.

Abstract

The design of a broad application tumor vaccine requires the identification of tumor antigens expressed in a majority of tumors of various origins. We questioned whether the major stress-inducible heat shock protein Hsp70 (also known as Hsp72), a protein frequently overexpressed in human tumors of various histological origins, but not in most physiological normal tissues, constitutes a tumor antigen. We selected the p391 and p393 peptides from the sequence of the human inducible Hsp70 that had a high affinity for HLA-A*0201. These peptides were able to trigger a CTL response in vivo in HLA-A*0201-transgenic HHD mice and in vitro in HLA-A*0201+ healthy donors. p391- and p393-specific human and murine CTL recognized human tumor cells overexpressing Hsp70 in a HLA-A*0201-restricted manner. Tetramer analysis of TILs showed that these Hsp70 epitopes are targets of an immune response in many HLA-A*0201+ breast cancer patients. Hsp70 is a tumor antigen and the Hsp70-derived peptides p391 and p393 could be used to raise a cytotoxic response against tumors of various origins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / chemistry
  • Blotting, Western
  • CD8-Positive T-Lymphocytes / metabolism
  • COS Cells
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Epitopes / chemistry
  • HLA Antigens / chemistry
  • HLA-A Antigens / chemistry*
  • HLA-A2 Antigen
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Immunotherapy / methods*
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Transgenic
  • Peptides / chemistry
  • Plasmids / metabolism
  • T-Lymphocytes, Cytotoxic / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, Neoplasm
  • Epitopes
  • HLA Antigens
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • HSP70 Heat-Shock Proteins
  • Peptides
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma