Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer.
We previously identified three novel HLA-A24-restricted epitope peptides, which were derived from three cancer-testis antigens, TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3), as targets for cancer vaccination against esophageal squamous cell carcinoma (ESCC). To examine the safety, immunogenicity, and antitumor effect of vaccine treatment using a combination of these three peptides, 10 HLA-A2402-positive advanced ESCC patients who failed to standard therapy were enrolled in a phase I clinical trial. Each of the three peptides (1 mg each) was intradermally administered with 1 mL of incomplete Freund's adjuvant to the neck in three separate regions weekly for 5 weeks. The cancer vaccination therapy was well tolerated without any treatment-associated adverse events of grade 3 or 4. The TTK-, LY6K-, and/or IMP-3-specific T-cell immune responses were observed by enzyme-linked immunospot assay in peripheral blood lymphocytes obtained from nine of the 10 ESCC patients after their vaccination. The median survival time after the vaccination was 6.6 months. The vaccination could induce good clinical responses in 50% of the 10 patients. One patient experienced a complete response in hepatic metastasis lasting 7 months, one showed objective responses in all lung metastasis lesions, and three patients revealed a stable disease condition for at least 2.5 months. The cancer vaccine therapy using these three peptides demonstrated satisfactory safety and good immunogenicity as well as promising disease control rate, and therefore warrants further clinical studies.
Kono
Koji
K
First Department of Surgery, University of Yamanashi, Yamanashi, Japan. kojikono@yamanashi.ac.jp
Mizukami
Yoshiki
Y
Daigo
Yataro
Y
Takano
Atsushi
A
Masuda
Ken
K
Yoshida
Koji
K
Tsunoda
Takuya
T
Kawaguchi
Yoshihiko
Y
Nakamura
Yusuke
Y
Fujii
Hideki
H
D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D004938:Esophageal Neoplasms / Q000276:immunology*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005620:Freund's Adjuvant / Q000276:immunology; D015234:HLA-A Antigens / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D053208:Kaplan-Meier Estimate; D008055:Lipids / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D008055:Lipids; D010446:Peptide Fragments; C114843:incomplete Freund's adjuvant; D005620:Freund's Adjuvant