Masahiko Sugiyama, Yoshihiro Kakeji, Shunichi Tsujitani, Yui Harada, Mitsuho Onimaru, Kumi Yoshida, Sakura Tanaka, Yasunori Emi, Masaru Morita, Yosuke Morodomi, Mamoru Hasegawa, Yoshihiko Maehara, Yoshikazu Yonemitsu
Malignant ascitis (MA) is a highly intractable and immunotherapy-resistant state of advanced gastrointestinal and ovarian cancers. Using a murine model of MA with CT26 colon cancer cells, we here determined that the imbalance between the VEGF-A/vascular permeability factor and its decoy receptor, soluble fms-like tryrosine kinase receptor-1 (sFLT-1), was a major cause of MA resistance to dendritic cell (DC)-based immunotherapy. We found that the ratio of VEGF-A/sFLT-1 was increased not only in murine but also in human MA, and F-gene-deleted recombinant Sendai virus (rSeV/dF)-mediated secretion of human sFLT-1 by DCs augmented not only the activity of DCs themselves, but also dramatically improved the survival of tumor-bearing animals associated with enhanced CTL activity and its infiltration to peritoneal tumors...
March 2011: Molecular Cancer Therapeutics