Basic research of cancer immunotherapy by using dendritic cells and clinical applications for head and neck tumors ; by using galactosylceramide

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16591980
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: TOHOKU UNIVERSITY
• Principal Investigator: HASHIMOTO Wataru Tohoku University, Hospital, Assistant Professor, 病院, 助手 (30323033)
• Co-Investigator(Kenkyū-buntansha): MORIKAWA Hidehiro Tohoku University, Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 助手 (60302155)
• Project Period (FY): 2004 – 2005
• Keywords: galactosylceramide / antitumor effect / natural killer T cells / IFN-γ / apoptosis / dendritic cells / innate immunity / head and neck tumor

Research Abstract

Dendritic cells (DCs) are specialized APCs which have an effective antitumor immuno response. DCs are expected to using cancer immunotherapy. A glycolipid antigen, α-Galactosylceramide(α-GalCer) is presented by a class Ib molecule, CD1d, and stimulates V α14 NKT cells, resulting in a rapid induction of IL-4 and IFN-γ.
We have investigated the antitumor effects of α-GalCer clarified that intratumoral onjection with α-GalCer treated-DCs resulted in regression of day 7 established poorly immunogenic tumors. We also clarified that these antitumor effects of α-GalCer treated-DCs were almost reduced in V α14NKT-deficient mice, suggesting that V α14 NKT cells are sufficient for these antitumor effects.
In this project, we investigated the antitumor effects of α-GalCer in human model in detail. Phenotypic analysis revealed an expansion of CD56+ CD161+ CD3+Vα24 TCR NKTcells on PBMC. These results suggest that NKT cells are also effector cells for α-GalCer -induced tumor apoptosis on human model.
Next, we analyzed a response to α-GalCer on PBMC from oral cancer patient. We collected patients' PBMC before and after chemotherapy, and investigated changes of NK or NKT cells. In this study, we have applied to committee of Tohoku University Hospital for the clinical application and were permitted. Then, we have started to collect clinical samples and got some samples. But we cannot analyze data because sample numbers were not so much. We hope that we will continue collecting samples from cancer patients and develop cancer immunotherapy by using α-GalCer treated-DCs.