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

✍ Scribed by Olivier Faure; Stéphanie Graff-Dubois; Laurent Bretaudeau; Laurent Derré; David-Alexandre Gross; Pedro M. S. Alves; Sébastien Cornet; Marie-Thérèse Duffour; Salem Chouaib; Isabelle Miconnet; Marc Grégoire; Francine Jotereau; François A. Lemonnier; Jean-Pierre Abastado; Kostas Kosmatopoulos

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: French
• Weight: 259 KB
• Volume: 108
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.11653

✦ Synopsis

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. © 2003 Wiley‐Liss, Inc.