title: Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA-A*0201-restricted epitopes.
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.
authors.affiliation: INSERM U487, Institut Gustave Roussy, Villejuif, France. olivier.faure@mines-paris.org
authors.forename: Olivier
authors.initials: O
authors.lastname: Faure
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Graff-Dubois
authors.forename: Laurent
authors.initials: L
authors.lastname: Bretaudeau
authors.forename: Laurent
authors.initials: L
authors.lastname: Derré
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Gross
authors.forename: Pedro M S
authors.initials: PM
authors.lastname: Alves
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cornet
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Duffour
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miconnet
authors.forename: Marc
authors.initials: M
authors.lastname: Grégoire
authors.forename: Francine
authors.initials: F
authors.lastname: Jotereau
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
authors.forename: Kostas
authors.initials: K
authors.lastname: Kosmatopoulos
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D019556:COS Cells; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry; D006680:HLA Antigens / Q000737:chemistry; D015234:HLA-A Antigens / Q000737:chemistry*; D015789:HLA-A2 Antigen; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000939:Epitopes; D006680:HLA Antigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma