A novel cancer immunotherapy with down-regulation of regulatory T cells using pretreatment of mild bone marrow suppression.
| Project/Area Number |
18591474
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Kyoto Prefectural University of Medicine |
|---|
Principal Investigator |
ITOH Tsuyoshi Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Assistant Professor (40420707)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YAMAGISHI Hisakazu Kyoto Prefectural University of Medicine, President (40128723)
上田 祐二 京都府立医科大学, 医学研究科, 講師 (60254356)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥2,040,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
|
|---|
| Keywords | Colorectal Surgery / Cancer vaccine |
|---|
| Research Abstract |
(1) An effect of mild immunosuppression was observed in mice administered cyclophosphamide. Cytotoxic T lymphocyte (CTL) response was enhanced in mice with this pretreatment possibly due to the down regulation of regulatory T cells which is considered to drive T helper-2 (112) immune response.
(2) The administration of anti-CD40 ligand monoclonal antibody (mAb) augmented this CTL response.
(3) Cancer vaccine protocol using the pretreatment of cyclophosphamide and the administration of a CD40L was evaluated as for its CTL response as well as anti tumor effect. C57B1/6 mice immunized with S11NFEKT peptide using this vaccine protocol were challenged with B16-0UA tumor cell lines. An enhancement of peptide-specific CTL response and anti tumor effect was observed. Its anti tumor effect was strongest in mice immunized with peptide concomitantly given cyclophosphamide and a-CD4OL Although some response was demonstrated in mice immunized with peptide alone, cyclophosphamide and a-CD40L elicited more strong peptide specific CM response and rejected tumor challenged after vaccination.
In conclusion, pretreatment of cyclophophamide and a-CD40L aiming at the down regulation of regulatory T cells enhanced peptide specific T cell response and effectively elicited anti tumor response. This vaccine protocol may be the break through for optimal cancer vaccine therapy.
|
Report
(3 results)
Research Products
(23 results)
