Oncolytic virus-initiated protective immunity against prostate cancer

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71 Citations (Scopus)

Abstract

Recently reovirus-based oncotherapy has been successfully implemented for the treatment of prostate cancer. In this report, we show that apart from its primary direct cancer-killing activity, reovirus oncotherapy overrides tumor-associated immune evasion strategies and confers protective antiprostate cancer immunity. Prostate cancer represents an ideal target for immunotherapies. However, currently available immune interventions fail to induce clinically significant antiprostate cancer immune responses, owing to the immunosuppressive microenvironment associated with this disease. We show here that during the process of oncolysis, reovirus acts upon prostate cancer cells and initiates proinflammatory cytokines and major histocompatibility complex (MHC) class I molecule expression. In an immunocompetent transgenic adenocarcinoma of mouse prostate (TRAMP) model, reovirus oncotherapy induces the homing of CD8 T and NK cells in tumors and the display of tumor-associated antigens (TAAs) on antigen-presenting cells (APCs), and endows dendritic cells (DCs) with a capacity to successfully present TAAs to tumor-specific CD8 T cells. These newly generated immunological events lead to the development of strong antiprostate cancer T cell responses, which restrict the growth of subsequently, implanted syngeneic tumor in an antigen-specific, but reovirus-independent manner. Such reovirus-initiated antiprostate cancer immunity represents a clinically valuable entity that can promote long-term cancer-free health even after discontinuation of the primary oncotherapy.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalMolecular Therapy
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 2011

Bibliographical note

Funding Information:
This work was supported by an operating grant from the Canadian Cancer Society Research Institute (CCSRI) through the Terry Fox Foundation, and Canadian Institutes for Health Research (CIHR) to P.W.K.L. S.A.G. and D.P. receive postdoctoral and doctoral fellowships, respectively, from the Cancer Research Training Program (CRTP).

ASJC Scopus Subject Areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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