| Co-Investigator(Kenkyū-buntansha) |
UENO Hikaru University of Occupational and Environmental Health, Department of Biochemistry and Molecular Pathophysiology, School of Medicine Prof, 医学部, 教授 (50260378)
江藤 正俊 九州大学, 医学部・附属病院, 助手 (90315078)
尾本 和也 東京女子医科大学, 助手
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
As-basic research, we constructed an adenovirus vector encoding a soluble VEGF receptor/flt-1 (Adflt-ExR). This soluble receptor is secreted from Adflt-ExR-transfected cells. Murine renal cell carcinoma cell line, Renca cells or murine bladder carcinoma cell line, MBT2 cells were infected with Adflt-ExR beforehand and injected subcutaneously into BALB/c or C3H/He mice, respectively. in vivo growth of AdVEGF-ExR-infected tumor cell lines was significantly suppressed in syngeneic mice. Although two of five mice rejected the AdVEGF-ExR infected RENCA, tumor-specific cytotoxic T lymphocytes were not generated from their spleen cells, suggesting no elicitation of cellular immune response. Our results indicate that adenovirus-mediated expression of a soluble VEGF receptor can be an effective therapy for cancer treatment, but that VEGF-targeted gene therapy is not necessarily accompanied with subsequent anti-tumor T cell immunity.
As clinical research, serum VEGF and FGF concentrations were me
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asured in 57 RCC patients using the sandwich enzyme immunoassay. Although these factors showed no significant correlation with tumor size, TNM stage, subsequent recurrence or disease progression, a significantly high VEGF level was observed in V(+) patients compared with V(-) patients. In addition, microarray analysis of renal cell carcinomas also demonstrates high expression of VEGF and ECGF1 genes compared with normal kidney tissues. We also performed combined immunotherapy with IFN-α, 5-FU, Leucovorin, cimetidine in 37 patients with advanced renal cell carcinoma, since IFN-α and 5-FU were recently reported to have antiangiogeneic effects against cancers. Response rate (CR + PR) was 16.2 % 12 weeks after the beginning of the treatment, and 56.8 % of patients showed 【greater than or equal】 NC (CR + PR + NC). In addition, 1 or 3 year survival of the patients with 【greater than or equal】 NC was 90.0 % or 56.4 %, respectively. These results demonstrate the efficacy of our combined immunotherapy for advanced renal cell carcinoma. Less
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