| 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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