Oncolytic Sendai virus-induced tumor-specific immunoresponses suppress "simulated metastasis" of squamous cell carcinoma in an immunocompetent mouse model

Head Neck. 2019 Jun;41(6):1676-1686. doi: 10.1002/hed.25642. Epub 2019 Jan 8.

Abstract

Background: The objectives of this study were to demonstrate anti-metastatic effect of BioKnife, uPA activity-dependent oncolytic Sendai virus, after BioKnife treatment for primary tumor, and analyze its mechanisms in a simulated metastasis mouse model of head and neck squamous cell carcinoma (HNSCC).

Methods: We established a simulated metastasis mouse model using a murine HNSCC cell line "SCCVII." We assessed a tumor size and an induction of tumor-specific immunoresponses using cytotoxic T-lymphocyte (CTL) assay, flow cytometry (FCM) in spleen and immunohistochemistry (IHC) in secondary tumor.

Results: Secondary tumors were significantly smaller in BioKnife-treated group. CTL activities were significantly improved in BioKnife group. FCM revealed that induction of dendritic cells and CD4+ /CD8+ lymphocytes was significantly higher in BioKnife group. IHC showed that CD8+ lymphocytes invaded secondary tumor.

Conclusion: Tumor-specific immunoresponses induced by BioKnife has great potential to be a novel, safe, and less invasive option for control and prevention of metastasis.

Keywords: Sendai virus; antitumor immune response; head and neck squamous cell carcinoma; metastasis; oncolytic virotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / therapy*
  • Cell Line, Tumor
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / therapy*
  • Immunocompetence
  • Mice, Inbred C3H
  • Oncolytic Virotherapy*
  • Oncolytic Viruses / physiology*
  • Sendai virus / physiology*
  • Urokinase-Type Plasminogen Activator
  • Xenograft Model Antitumor Assays

Substances

  • Urokinase-Type Plasminogen Activator