| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
(1) We examined phase I clinical trial of DC-tumor fusion vaccine in gastrointestinal cancer patients with advanced or recurrent stage. This study was approved in the ethics committee of our university. Primary endpoint of this study was safety and secondary endpoints were induction of anti-tumor immunity and clinical responses. Thirteen patients with Stage IV or recurrent gastrointestinal cancer were enrolled in this study after informed consent was obtained. Tumor cells were cryopreserved following acquisition from the primary or a metastatic site. DCs were induced from mononuclear cells of patients by culture with cytokines (GM-CSF, IL-4, TNF-alpha, IL-1 beta, IL-6 and PGE2). Fusion of irradiated tumor cells and DC was created with a combination of PEG and electrofusion (two-step fusion method). At 2 week interval, patients received 4 freshly prepared fusion vaccines, with a constant dose range of 1X107 to 4X107 cells. Serious adverse events were not observed in any of the enrolled patients and all Common Toxicity Criteria were grade I. Clinical responses to date are 1 with PR, 5 with SD and 7 with progressive disease. In patients with PR or SD, a shift to Thl in ThliTh2 balance and a decrease of immunosuppressive factors (IAP, TGF-beta, CD4+CD25+) were demonstrated. These results suggests that a strategy of fusion vaccine employing auto-DC fused with auto-tumor cells in patients with stage IV and recurrent gastrointestinal cancer is feasible and may demonstrate evidence of tumor response.(2) We examined the combination therapy of fusion vaccine and chemotherapy (TS-1, 5-FU, CDDP). The number of lung metastasis in mice administered with combination of fusion cells and TS-1, 5-FU or CDDP decreased significantly as compared with TS-1, 5-FU or CDDP alone. These results suggested that the superior therapeutic effects of immuno-chemotherapy with fusion vaccine and TS-1, 5-FU or CDDP.
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