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J Immunother. 2019 Sep;42(7):244-250. doi: 10.1097/CJI.0000000000000274.

Identification of a Promiscuous Epitope Peptide Derived From HSP70.

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Departments of Gastroenterological, Breast, and Endocrine Surgery.
Translational Research and Developmental Therapeutics against Cancer.
Immunology, Yamaguchi University Graduate School of Medicine.
Department of Immunology, Kochi Medical School, Kochi.
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto.
NEC Corporation, Tokyo.
Yamaguchi University Hospital Cancer Center, Yamaguchi.
Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Japan.


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.

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