Double trouble for tumours: Exploiting the tumour microenvironment to enhance anticancer effect of oncolytic viruses |
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| Authors: | Naomi De Silva Harold Atkins David H. Kirn John C. Bell Caroline J. Breitbach |
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| Affiliation: | 1. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada;2. Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, Canada;3. Jennerex Inc., San Francisco, CA, USA;1. Biodesign Center for Immunotherapy, Vaccines, and Virotherapy (B-CIVV), The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA;1. Leeds Institute of Cancer and Pathology, St. James’ University Hospital, Leeds, UK;2. Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA;3. Oncolytics Biotech Incorporated, Calgary, Alberta, Canada;4. The Institute of Cancer Research, London, UK;5. Department of Microbial and Cellular Sciences, University of Surrey, Guildford, UK;6. Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA;1. Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA;2. Center for Gene Therapy, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA;3. Gene Editing and Viral Vector Core, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA;1. Instituto Cavanilles de Biodiversidad y Biologia Evolutiva and Departament de Genètica, Universitat de València, Valencia, Spain;2. Department of Biological Sciences, University of North Carolina at Charlotte, Charlotte, NC, USA |
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| Abstract: | Oncolytic viruses (OVs) are selected based on their ability to eliminate malignancies by direct infection and lysis of cancer cells. Originally, OVs were designed to target malignancies by taking advantage of the defects of cancer cells observed in vitro. Subsequent analysis of virus delivery and spread in vivo has demonstrated that the tumour microenvironment can impede the ability of OVs to effectively infect and spread. Despite this limitation, it is becoming increasingly evident that OVs are also able to take advantage of certain features of the tumour microenvironment. Currently, a growing body of the literature is delineating the complex interaction between OVs and the tumour microenvironment that results in an additional therapeutic activity; these viruses are able to target malignancies by rapidly altering the tumour microenvironment into a milieu that potentiates anticancer activity. Herein, we discuss strategies that capitalize on the multifaceted relationship between OVs and host–tumour interactions that enhance the toxicity of OVs to the tumour microenvironment. |
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