Identification of a Promiscuous Epitope Peptide Derived From HSP70

• Published in: Journal of immunotherapy (1997) Vol. 42; no. 7; p. 244
• Main Authors: Matsui, Hiroto, Hazama, Shoichi, Tamada, Koji, Udaka, Keiko, Irie, Atsushi, Nishimura, Yasuharu, Miyakawa, Tomoya, Doi, Shun, Nakajima, Masao, Kanekiyo, Shinsuke, Tokumitsu, Yukio, Shindo, Yoshitaro, Tomochika, Shinobu, Yoshida, Shin, Iida, Michihisa, Suzuki, Nobuaki, Takeda, Shigeru, Yamamoto, Shigeru, Yoshino, Shigefumi, Ueno, Tomio, Nagano, Hiroaki
• Format: Journal Article
• Language: English
• Published: United States 01.09.2019
• ISSN: 1537-4513
• DOI: 10.1097/cji.0000000000000274

We previously found that heat-shock protein 70 (HSP70) is expressed on hepatocellular carcinoma cells and developed an HSP70 mRNA-transfected dendritic cell therapy for treating unresectable or recurrent hepatocellular carcinoma. The phase I trial was completed successfully. The purpose of this study is to identify a promiscuous epitope peptide derived from HSP70 for the purpose of developing a novel cancer peptide vaccine. Using a computational algorithm to analyze the specificity of previously reported major histocompatibility complex class I-binding peptides, we selected candidates that bound to >2 of the 3 HLA types. Twenty-nine HSP70-derived peptides (9-mers) that bound to HLA-class I was selected. The peptides were prioritized based on the results of peptide binding experiments. Using dendritic cells stimulated with the candidate peptide described previously as stimulators and CD8 T cells as effectors, an ELISPOT assay was performed. Cytotoxicity of CD8 lymphocytes stimulated with the candidate peptides toward HSP70-expressing cancer cells was analyzed using an xCELLigence System. Peptides were administered to HLA-A 24 transgenic mice as vaccines, and peptide-specific T-cell induction was measured in vivo. We identified a multi-HLA-class I-binding epitope peptide that bound to HLA-A*02:01, *02:06, and *24:02 in vitro using an interferon-γ ELISPOT immune response induction assay. Cytotoxicity was confirmed in vitro, and safety and immune response induction were confirmed in vivo using HLA-A 24 transgenic mice. Our study demonstrated that the promiscuous HSP70-derived peptide is applicable to cancer immunotherapy in patients with HLA-A*24:02-positive, *02:01-positive, and *02:06-positive HSP70-expressing cancers.