| Project/Area Number |
16592006
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Surgical dentistry
|
|---|
| Research Institution | The University of Tokushima |
|---|
Principal Investigator |
YOSHIDA Hideo The University of Tokushima, Graduate School, Institute of Health Bioscience, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (30116131)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
OKAMOTO Masato The University of Tokushima, Graduate School, Institute of Health Bioscience, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 助手 (10243718)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | Cancer Immunotherapy / dendritic cell / OK-432 / TS-1 / Toll-loke receptor / lipoteichoic acid-related molecule OK-PSA / clinical trial / 細胞免疫療法 / OK-432 / Toll-like receptor 4 (TLR4) |
|---|
| Research Abstract |
Dendritic cells (DCs) are professional antigen-presenting cells. Adequately matured DCs can stimulate T cells to induce tumor-specific cytotoxic T lymphocytes (CTLs). A streptococcal anticancer immunotherapeutic agent OK-432 can strongly mature DCs. In tumor-bearing mouse model, radiation therapy (RT) or oral administration of anticancer drug TS-1 followed by an intratumoral injection of syngeneic bone-marrow-derived DCs and of OK-432 resulted in inducing CTLs and in inhibiting tumor growth. The therapy did not elicit any significant effects in tumor-bearing mice in which Toll-like receptor (TLR) 4 is mutated. We have already succeeded in isolating an active component of OK-432 (lipoteichoic acid-related molecule OK-PSA). OK-PSA matured DCs far better, than original OK-432 in vitro, and OK-PSA-treated DCs stimulated allogeneic T cells to produce IFN-γ, and to induce allo-antigen specific CTLs. In in vivo model, TS-1+DCs+OK-PSA therapy exhibited anticancer effect stronger than the therapy using TS-1, DCs and OK-432. Based on these basic data, we have started an early stage clinical trial, "the therapy with an intratumoral administration of DCs in combination with TS-1 and OK-432", in oral cancer patients in which the standard therapies were not effective. Of 5 cases, complete remission (CR) was observed in one case, partial remission (PR) in 3 cases, and stable desease (SD) in one case. No significant toxicity over grade 3 was observed. It was strongly suggested that an intratumoral administration in combination with TS-1 and OK-432 is safety and effective in oral cancer patients.
|
