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Abstract

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.

Journal

  • Molecular Cancer Therapeutics

    Molecular Cancer Therapeutics 10(3), 540-549, 2011-03-01

    American Association for Cancer Research

Codes

  • NII Article ID (NAID)
    120004951600
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    1535-7163
  • Data Source
    IR 
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