Inhibitory effect of the polyinosinic-polycytidylic acid/cationic liposome on the progression of murine B16F10 melanoma

Taku Fujimura, Satoshi Nakagawa, Tomoyuki Ohtani, Yumiko Ito, Setsuya Aiba

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Cellular proteins, retinoic acid inducible gene-I and Toll-like receptor 3, sense dsRNA including polyinosinic-polycytidylic acid (PIC) to stimulate innate immune response. The local administration of PIC has been demonstrated to be effective in anti-tumor immunotherapy. However, the effects of PIC delivered cross the cell membrane have not yet been examined. To address this issue, we used a complex of PIC and cationic liposome (PIC liposome) and examined its anti-tumor effects in vitro and in vivo. PIC liposome could directly suppress the growth of B16F10 melanoma in vitro and repeated peritumoral injections of PIC liposome inhibited melanoma growth in a dose-dependent manner. This treatment induced tyrosinase-related protein-2 (TRP-2)-tetramer+ CD8+ cells in the lymph nodes. As the mechanism for its anti-tumor immune response, we showed that the intradermal injection of PIC liposome induced the maturation of dendritic cells (DC). Moreover, the intratumoral injection of immature DC after treatment with PIC liposome significantly increased the number of TRP-2-specific IFN-γ-producing cells in the lymph nodes as well as spleen, which resulted in an augmentation of the anti-tumor immune response. These studies demonstrate the potential of peritumoral injection of PIC liposome as immunotherapy for malignant melanoma.

Original languageEnglish
Pages (from-to)3371-3380
Number of pages10
JournalEuropean Journal of Immunology
Volume36
Issue number12
DOIs
Publication statusPublished - 2006 Dec

Keywords

  • Dendritic cell
  • Immunotherapy
  • Liposome
  • Melanoma
  • Poly IC

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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