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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
12:42

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

Tumor infection by oncolytic reovirus primes adaptive antitumor immunity

Robin J Prestwich1, Fiona Errington, Elizabeth J Ilett

  • 1Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, United Kingdom.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|November 18, 2008
PubMed
Abstract

Insights

Reovirus infection of tumors not only kills cancer cells but also stimulates the immune system to fight cancer. This dual action suggests reovirus as a promising cancer immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Virology

Background:

  • Reovirus is being investigated for direct cancer-killing (oncolytic) effects.
  • The potential for reovirus to stimulate adaptive antitumor immunity is not fully understood.

Purpose of the Study:

  • To determine if reovirus infection of tumors can generate bystander, adaptive antitumor immunity.
  • To assess reovirus's impact on tumor burden, immune cell priming, and cytokine responses.

Main Methods:

  • Intravenous reovirus administration in mice with melanoma lymph node metastases.
  • Assessment of tumor clearance, T-cell responses to tumor antigens, and cytokine production.
  • In vitro human cell assays investigating dendritic cell maturation and T-cell priming by reovirus-infected melanoma cells.

Main Results:

  • Reovirus reduced metastatic lymph node burden and induced antitumor immunity in mice.
  • Reovirus-infected melanoma cells matured dendritic cells and primed cytotoxic T lymphocytes (CTLs) in vitro.
  • These CTLs demonstrated specific cytotoxicity against human melanoma cells and cross-primed CD8+ T cells.

Conclusions:

  • Reovirus infection of tumor cells effectively reduces metastatic disease and primes the immune system for an antitumor response.
  • Clinical trials should consider both the direct oncolytic and immunotherapeutic benefits of reovirus.

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