Phase I trial of multidrug resistance-associated protein 3-derived peptide in patients with hepatocellular carcinoma.
Multidrug resistance-associated protein 3 (MRP3) is a carrier-type transport protein belonging to the ABC transporters. In this study, we investigated the safety and immunogenicity of a MRP3-derived peptide (MRP3765) as a vaccine and characterized the MRP3-specific T cell responses induced. Twelve hepatocellular carcinoma (HCC) patients treated with hepatic arterial infusion chemotherapy (HAIC) were enrolled. The MRP3-derived peptide was emulsified in incomplete Freund's adjuvant and administered via subcutaneous immunization three times weekly. No serious adverse drug reactions to the peptide vaccine were observed, and the vaccination was well tolerated. The vaccination induced MRP3-specific immunity in 72.7% of the patients. In a phenotypic analysis, the largest post-vaccinated increase in MRP3-specific T cells was due to an increase in cells with the effector memory phenotype. Among the 12 patients, one patient showed a partial response, nine showed a stable disease, and two showed a progressive disease. The median overall survival time was 14.0 months. In conclusion, the safety, effects of immune boosting, and possible prolongation of overall survival by the MRP3-derived peptide demonstrate the potential of the peptide to provide clinical benefit in HCC patients.
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Eishiro
E
Mizukoshi
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Hidetoshi
H
Nakagawa
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Masaaki
M
Kitahara
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Tatsuya
T
Yamashita
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Kuniaki
K
Arai
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Hajime
H
Sunagozaka
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Noriho
N
Iida
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan.
Kazumi
K
Fushimi
Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Ishikawa 920-8641, Japan. Electronic address: skaneko@m-kanazawa.jp.
Shuichi
S
Kaneko
D000368:Aged; D019496:Cancer Vaccines / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination
D019496:Cancer Vaccines; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010446:Peptide Fragments; C114462:multidrug resistance-associated protein 3
Cancer; Chemotherapy; Cytotoxic T cell; Epitope; Immunotherapy