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
INSERM U487, Institut Gustave Roussy, Villejuif, France.
Int J Cancer. 2004 Mar 1;108(6):863-70. 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-A0201. These peptides were able to trigger a CTL response in vivo in HLA-A0201-transgenic HHD mice and in vitro in HLA-A0201+ healthy donors. p391- and p393-specific human and murine CTL recognized human tumor cells overexpressing Hsp70 in a HLA-A0201-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.
一种广泛应用的肿瘤疫苗的设计需要鉴定在大多数不同起源的肿瘤中表达的肿瘤抗原。我们质疑主要的应激诱导热休克蛋白Hsp70（也称为Hsp72），一种在各种组织学起源的人类肿瘤中经常过度表达，但在大多数生理正常组织中不表达的蛋白质，是否构成一种肿瘤抗原。我们从人诱导型Hsp70的序列中选择了对HLA-A0201具有高亲和力的p391和p393肽段。这些肽段能够在体内的HLA-A0201转基因HHD小鼠中以及在体外的HLA-A0201+健康供体中引发CTL反应。p391和p393特异性的人和鼠CTL以HLA-A0201限制性方式识别过表达Hsp70的人肿瘤细胞。对肿瘤浸润淋巴细胞（TILs）的四聚体分析表明，这些Hsp70表位是许多HLA-A*0201+乳腺癌患者免疫反应的靶点。Hsp70是一种肿瘤抗原，源自Hsp70的肽段p391和p393可用于引发针对各种起源肿瘤的细胞毒性反应。
