Phase I clinical trial of cancer vaccine using adjuvant for activation of immunity

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17390376
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: HOKKAIDO UNIVERSITY (2006); Jikei University School of Medicine (2005)
• Principal Investigator: MIYAMOTO Masaki Hokkaido University, Hokkaido University Hospital, Assistant, 病院, 助手 (40333611)
• Co-Investigator(Kenkyū-buntansha): MORIKAWA Toshiaki Jikei University, Medical Department, Professor, 医学部, 教授 (60292025) ; KONDO Satoshi Hokkaido University, Graduate School of medicine, Professor, 大学院医学研究科, 教授 (30215454) ; AKITA Hirotoshi Hokkaido University, Graduate School of medicine, Professor, 大学院医学研究科, 教授 (70222528) ; NISHIMURA Takashi Hokkaido University, Institute for Genetic Medicine, Professor, 遺伝子病制御研究所, 教授 (30143001) ; IKEDA Hiroaki Hokkaido University, Institute for Genetic Medicine, Assistant Professor, 遺伝子病制御研究所, 助教授 (40374673)
• Project Period (FY): 2005 – 2006
• Keywords: advanced cancer / cancer vaccine / immuno-therapy / NY-ESO-1 / adjuvant

Research Abstract

We screened NY-ESO-1 expression by using immunohistochemistry in 122 patients with esophageal cancer or 80 patients with pancreatic cancer at Hokkaido University Hospital. Initially, we clarified that esophageal cancer cell line HEC46 expresses NY-ESO-1 by RT-PCR and its xenograft tumor from SCID mause is useful as a positive control for immunohistochemistry of NY-ESO-1. On the other hand, it was clarified that TE8 does not express NY-ESO-1 by RT-PCR and its xenograft tumor is useful as a negative control. Twenty-two patients of esophageal cancer had NY-ESO-1 expressing tumor but no one of pancreatic cancer had NY-ESO-1 expressing tumor. NY-ESO-1 positive esophageal tumors had larger number of CD4 positive T cells and CD8 positive T cells compared to NY-ESO-1 negative tumors. Survival of patients with NY-ESO-1 positive esophageal tumor was significantly better than that with negative tumor in stage III and IV cases. Moreover, Survival of patients who have esophageal tumors with many CD40 positive B cells was worse but the number of FoxP3 positive lymphocytes had no effects for survival of patients.
Therefore, induction of infiltration of CD4 positive T cells and CD8 positive T cells could be introduced as an effective cancer vaccine targeted NY-ESO-1. CpG motief is used as an adjuvant for activation of immunity. NY-ESO-1 protein was obtained from Ludwig institute in USA, and CpG was from Pfizer US. After then, phase I clinical trial was started. Even if patients have any types of tumor, they could enter this study when they agreed informed consent. Till now, 4 patients agreed for entry and 1 received vaccination. However, 3 patients could not enter this study because of their poor performance status. No side effect was seen