Antagonism of VEGF by genetically engineered dendritic cells is essential to induce antitumor immunity against malignant ascites

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

研究成果: Contribution to journalArticle

11 被引用数 (Scopus)

抄録

Malignant ascitis (MA) is a highly intractable and immunotherapy-resistant state of advanced gastro-intestinal 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. These findings were not seen in immunodeficient mice, indicating that a VEGF-A/sFLT-1 imbalance is critical for determining the antitumor immune response by DC-vaccination therapy against MA.

本文言語英語
ページ(範囲)540-549
ページ数10
ジャーナルMolecular cancer therapeutics
10
3
DOI
出版ステータス出版済み - 3 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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