Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma

Masafumi Ikeda; Takuji Okusaka; Izumi Ohno; Shuichi Mitsunaga; Shunsuke Kondo; Hideki Ueno; Chigusa Morizane; Kazuto Gemmoto; Hideaki Suna; Yasunori Ushida; Junji Furuse

doi:10.2217/imt-2020-0278

Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma

Immunotherapy. 2021 Apr;13(5):371-385. doi: 10.2217/imt-2020-0278. Epub 2021 Feb 2.

Authors

Affiliations

¹ Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
² Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan.
³ Oncology Clinical Development Unit, Ono Pharmaceutical Co., Ltd, Osaka, Japan.
⁴ Clinical Development, Data Science, Statistical Analysis, Ono Pharmaceutical Co., Ltd, Osaka, Japan.
⁵ Department of Medical Oncology, Kyorin University Faculty of Medicine, Tokyo, Japan.

PMID: 33525928
DOI: 10.2217/imt-2020-0278

Abstract

Aim: Two peptide cocktail vaccines using glypican-3, WD-repeat-containing protein up-regulated in hepatocellular carcinoma (HCC) and nei endonuclease VIII-like three epitopes were evaluated in advanced HCC in two Phase I studies. Patients & methods: Study 1 evaluated dose-limiting toxicities (DLTs) of peptides 1-3 (HLA-A24-restricted) and study 2 evaluated DLTs of peptides 1-6 (HLA-A24 or A02-restricted). Results: Overall, 18 and 14 patients were enrolled in studies 1 and 2, respectively. No DLTs were observed up to 7.1 mg of the vaccine cocktail. No complete response/partial response was observed. Stable disease was reported in nine and five patients with a disease control rate of 52.9% and 35.7% in studies 1 and 2, respectively. Conclusion: Both vaccines showed good tolerability and potential usefulness against HCC. Clinical trial registration: JapicCTI-121933; JapicCTI-142477.

Keywords: GPC3; HCC; NEIL3; Phase I studies; WDRPUH; hepatocellular carcinoma.

Publication types

Clinical Trial, Phase I
Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antigens, Neoplasm / immunology
Cancer Vaccines / administration & dosage
Cancer Vaccines / adverse effects
Cancer Vaccines / immunology*
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / immunology
Carcinoma, Hepatocellular / pathology
Carrier Proteins / immunology*
Cilia / immunology*
Endpoint Determination
Epitopes / administration & dosage
Epitopes / adverse effects
Epitopes / immunology
Female
Glypicans / immunology*
HLA-A Antigens / immunology
Humans
Liver Neoplasms / drug therapy*
Liver Neoplasms / immunology
Liver Neoplasms / pathology
Male
Middle Aged
N-Glycosyl Hydrolases / immunology*
T-Lymphocytes, Cytotoxic / immunology
Treatment Outcome
Vaccines, Subunit / administration & dosage
Vaccines, Subunit / adverse effects
Vaccines, Subunit / immunology

Substances

Antigens, Neoplasm
CFAP52 protein, human
Cancer Vaccines
Carrier Proteins
Epitopes
GPC3 protein, human
Glypicans
HLA-A Antigens
Vaccines, Subunit
N-Glycosyl Hydrolases
NEIL3 protein, human