Vaccination with peptides derived from cancer‐testis antigens in combination with CpG‐7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma

• Published in: Cancer science 2010-12, Vol.101 (12), p.2510-2517
• Main Authors: Iwahashi, Makoto, Katsuda, Masahiro, Nakamori, Mikihito, Nakamura, Masaki, Naka, Teiji, Ojima, Toshiyasu, Iida, Takeshi, Yamaue, Hiroki
• Format: Article
• Language: English
• Subjects: Aged; Antigens, Ly - immunology; Antigens, Ly - therapeutic use; Antigens, Neoplasm - immunology; Antigens, Neoplasm - therapeutic use; Biological and medical sciences; Cancer Vaccines - immunology; Cancer Vaccines - therapeutic use; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Cycle Proteins - immunology; Cell Cycle Proteins - therapeutic use; Cell Separation; Cytokines - blood; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - immunology; Esophagus; Female; Flow Cytometry; Gastroenterology. Liver. Pancreas. Abdomen; GPI-Linked Proteins - immunology; GPI-Linked Proteins - therapeutic use; Humans; Male; Medical sciences; Middle Aged; Oligodeoxyribonucleotides - immunology; Oligodeoxyribonucleotides - therapeutic use; Original; Protein Serine-Threonine Kinases - immunology; Protein Serine-Threonine Kinases - therapeutic use; Protein-Tyrosine Kinases; Tumors; Vaccination - methods; Vaccines, Subunit - immunology; Vaccines, Subunit - therapeutic use
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2010.01732.x

Potent helper action is necessary for peptide‐based vaccines to efficiently induce antitumor immune responses against advanced cancer. A phase I trial for advanced esophageal squamous cell carcinoma was carried out for patients with HLA‐A*2402 using epitope peptides derived from novel cancer‐testis antigens, LY6K and TTK, in combination with CpG‐7909 (NCT00669292). This study investigated the feasibility and the toxicity as well as induction of tumor antigen‐specific immune responses. Nine patients were vaccinated on days 1, 8, 15, and 22 of each 28‐day treatment cycle with peptide LY6K‐177, peptide TTK‐567, and CpG‐7909 (level‐1; 0, level‐2; 0.02, level‐3; 0.1 mg/kg) and all were tolerated by this treatment. LY6K‐specific T cell responses in PBMCs were detected in two of the three patients in each level. In particular, two patients in level‐2/3 showed potent LY6K‐specific T cell responses. In contrast, only two patients in level‐2/3 showed TTK‐567‐specific T cell responses. The frequency of LY6K‐177 or TTK‐567‐specific CD8+ T cells increased in patients in level‐2/3 (with CpG). The vaccination with peptides and CpG‐7909 increased and activated both plasmacytoid dentritic cells and natural killer cells, and increased the serum level of α‐interferon. There were no complete response (CR) and partial response (PR), however, one of three patients in level‐1, and four of six patients in level‐2/3 showed stable disease (SD). In conclusion, vaccination with LY6K‐177 and TTK‐567 in combination with CpG‐7909 successfully elicited antigen‐specific CD8+ T cell responses and enhanced the innate immunity of patients with advanced esophageal squamous cell carcinoma. This vaccine protocol is therefore recommended to undergo further phase II trials. (Cancer Sci 2010; 101: 2510–2517)