Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA‐A0201‐restricted epitopes

• Published in: International journal of cancer 2004-03, Vol.108 (6), p.863-870
• Main Authors: Faure, Olivier, Graff‐Dubois, Stéphanie, Bretaudeau, Laurent, Derré, Laurent, Gross, David‐Alexandre, Alves, Pedro M. S., Cornet, Sébastien, Duffour, Marie‐Thérèse, Chouaib, Salem, Miconnet, Isabelle, Grégoire, Marc, Jotereau, Francine, Lemonnier, François A., Abastado, Jean‐Pierre, Kosmatopoulos, Kostas
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Neoplasm - chemistry; Antineoplastic agents; Biological and medical sciences; Blotting, Western; CD8-Positive T-Lymphocytes - metabolism; Cell Line, Tumor; COS Cells; cytotoxic T lymphocytes; Dose-Response Relationship, Drug; Epitopes - chemistry; heat shock protein (Hsp) 70; HLA Antigens - chemistry; HLA-A Antigens - chemistry; HLA-A2 Antigen; HLA‐A0201‐restricted epitope; HSP70 Heat-Shock Proteins - metabolism; Humans; Immunotherapy; Immunotherapy - methods; Interferon-gamma - metabolism; Medical sciences; Mice; Mice, Transgenic; Peptides - chemistry; Pharmacology. Drug treatments; Plasmids - metabolism; T-Lymphocytes, Cytotoxic - metabolism; tumor antigen; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11653

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.