Cancer Immunology, Immunotherapy

, Volume 57, Issue 1, pp 73–84

Intratumoral injection of inactivated Sendai virus particles elicits strong antitumor activity by enhancing local CXCL10 expression and systemic NK cell activation

  • Atsuko Fujihara
  • Masayuki Kurooka
  • Tsuneharu Miki
  • Yasufumi Kaneda
Original Article

Abstract

We have already demonstrated that inactivated, replication-defective Sendai virus particles (HVJ-E) have a powerful antitumor effect by both the generation of tumor-specific cytotoxic T cells and inhibition of regulatory T cell activity. Here, we report that HVJ-E also has an antitumor effect through non-T cell immunity. Microarray analysis revealed that direct injection of HVJ-E induced the expression of CXCL10 in established Renca tumors. CXCL10 was secreted by dendritic cells in the tumors after HVJ-E injection. Quantitative real-time RT-PCR and immunohistochemistry revealed that CXCR3+ cells (predominantly NK cells) infiltrated the HVJ-E-injected tumors. Moreover, HVJ-E injection caused systemic activation of NK cells and enhanced their cytotoxity against tumor cells. In an in vivo experiment, approximately 50% of tumors were eradicated by HVJ-E injection, and this activity of HVJ-E against Renca tumors was largely abolished by NK cell depletion using anti-asialo GM1 antibody. Since HVJ-E injection induced systemic antitumor immunity by enhancing or correcting the chemokine-chemokine receptor axis, it might be a potential new therapy for cancer.

Keywords

HVJ-E Antitumor immunity CXCL10 NK cell Dendritic cell 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Atsuko Fujihara
    • 1
    • 2
  • Masayuki Kurooka
    • 1
  • Tsuneharu Miki
    • 2
  • Yasufumi Kaneda
    • 1
  1. 1.Division of Gene Therapy ScienceOsaka University Medical School, Graduate School of MedicineSuitaJapan
  2. 2.Department of UrologyKyoto Prefectural University of MedicineKyotoJapan

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