Open AccessIdentification of a Promiscuous Epitope Peptide Derived From HSP70
Author(s) -
Hiroto Matsui,
Shoichi Hazama,
Koji Tamada,
Keiko Udaka,
Atsushi Irie,
Yasuharu Nishimura,
Tomoya Miyakawa,
S Doi,
Masahiro Nakajima,
Shinsuke Kanekiyo,
Yukio Tokumitsu,
Yoshitaro Shindo,
Shinobu Tomochika,
Shigeo Yoshida,
Michihisa Iida,
Nobuaki Suzuki,
Shigeru Takeda,
Shigeru Yamamoto,
Shigefumi Yoshino,
Takayoshi Ueno,
Hiroaki Nagano
Publication year - 2019
Publication title -
journal of immunotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.805
H-Index - 92
eISSN - 1537-4513
pISSN - 1524-9557
DOI - 10.1097/cji.0000000000000274
Subject(s) - elispot , epitope , cd8 , cytotoxic t cell , peptide , cancer immunotherapy , immunotherapy , human leukocyte antigen , biology , peptide vaccine , immune system , major histocompatibility complex , microbiology and biotechnology , cancer research , antigen , in vitro , immunology , biochemistry
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.