Project/Area Number |
12671272
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Tokyo Women 's Medical University |
Principal Investigator |
TAKASHI Hatori Tokyo Women's Medical University, Department.Gastroenterological Surgery,Instructor., 医学部, 助手 (50208550)
|
Project Period (FY) |
2000 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
Keywords | Dendritic cell / Immunotherapy / CTL |
Research Abstract |
Dendritic cells are well known as potent antigen-presenting cells. We performed the new cancer immunotherapy by using dendritic cells to inject intratumorally. Mouse dendritic cells were generated from bone marrow by 5 days in vitro culture with rGM-CSF plus IL-4.These DCs were then injected into the MT-901 mouse breast cancer which was inoculated s. c. 9 days before DC injection. The DC injection could inhibit the tumor growth not only the injected site but also other site which was not injected DCs. Direct injection of syhgeneic dendritic cells could inhibit the tumor growth but allogeneic DCs could not inhibit the tumor growth. When CD8 T cells were depleted by monoclonal antibody 48hr before DC injection, in vivo effect of tumor inhibition was disappeared. Splenocyte obtained from the mouse which received the DC injection demonstrated the tumor specific cytotoxicity and Type 1 cytokine release in tumor specific manner. Systemic administration of IL-2 after DC injection and KLH pulsation to DCs before injection could enhance the in vivo anti-tumor efficacy dominantly. Base on these data, we performed the clinical trials of dendritic cell injection therapy in the patients with advanced cancer. In 14 cases, only grade 1 fever was seen as toxicity. 4 of 15 patients received the tumor regression and 5 received the reduction of tumor marker. These results demonstrated that the dendritic injection therapy is the useful treatment for human canter and further study will be needed to proceed this new approach.
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