Concise Review: Targeting Cancer Stem Cells and Their Supporting Niche Using Oncolytic Viruses

Author:

Crupi Mathieu J.F.12,Bell John C.12,Singaravelu Ragunath12ORCID

Affiliation:

1. Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

2. Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada

Abstract

Abstract Cancer stem cells (CSCs) have the capacity to self-renew and differentiate to give rise to heterogenous cancer cell lineages in solid tumors. These CSC populations are associated with metastasis, tumor relapse, and resistance to conventional anticancer therapies. Here, we focus on the use of oncolytic viruses (OVs) to target CSCs as well as the OV-driven interferon production in the tumor microenvironment (TME) that can repress CSC properties. We explore the ability of OVs to deliver combinations of immune-modulating therapeutic transgenes, such as immune checkpoint inhibitor antibodies. In particular, we highlight the advantages of virally encoded bi-specific T cell engagers (BiTEs) to not only target cell-surface markers on CSCs, but also tumor-associated antigens on contributing components of the surrounding TME and other cancer cells. We also highlight the crucial role of combination anticancer treatments, evidenced by synergy of OV-delivered BiTEs and chimeric-antigen receptor T cell therapy. Stem Cells  2019;37:716–723

Funder

Canadian Cancer Society Research Institute

Canadian Institutes of Health Research

Ontario Institute of Cancer Research

Terry Fox Foundation

Ontario Institute for Cancer Research

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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