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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.

Author information

1
Departments of Gastroenterological, Breast, and Endocrine Surgery.
2
Translational Research and Developmental Therapeutics against Cancer.
3
Immunology, Yamaguchi University Graduate School of Medicine.
4
Department of Immunology, Kochi Medical School, Kochi.
5
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto.
6
NEC Corporation, Tokyo.
7
Yamaguchi University Hospital Cancer Center, Yamaguchi.
8
Department of Digestive Surgery, Kawasaki Medical School, Kurashiki, Japan.

Abstract

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.

PMID:
31398179
DOI:
10.1097/CJI.0000000000000274
Free PMC Article

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