Redirecting oncolytic viruses: Engineering opportunists to take control of the tumour microenvironment |
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| Institution: | 1. Centre for Innovative Cancer Research, Ottawa Hospital Research Institute, Ottawa, K1H 8L6, Canada;2. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada;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. Children’s Hospital of Eastern Ontario Research Institute, Apoptosis Research Center, Ottawa, ON, Canada;2. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada;1. Department of Biomedicine, Aarhus University, Aarhus, Denmark;2. Children’s Hospital of Eastern Ontario Research Institute, Apoptosis Research Center, Ottawa, ON, Canada;3. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada;1. Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy;2. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands;1. Cancer axis and Institut du cancer de Montréal, Centre de recherche du CHUM- CRCHUM, 900 St-Denis Street, Viger Tower, Room R10.480, Montreal, Quebec, H2X0A9, Canada;2. Département de Microbiologie, Infectiologie et Immunologie, Faculty of Medicine, Université de Montréal, 2900 Edouard-Montpetit Boulevard, Roger-Gaudry Building, Montreal, Quebec, H3T1J4, Canada;1. Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, N1G 2W1, Canada;2. Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, N1G 2W1, Canada;3. Juravinski Cancer Centre, 699 Concession Street, Hamilton, ON L8V 5C2, Canada |
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| Abstract: | The transformation of healthy cells to malignant often drives them to become inherently susceptible to viral infection as a trade-off to achieve uninhibited growth and immune escape. Enter oncolytic viruses (OVs), an exciting class of viruses that specifically infect cancer cells, leaving healthy tissue unharmed. Unfortunately, there is more to this story. Tumours are much more than a group of cancer cells, the surrounding tumour microenvironment (TME) comprises a collection of cells which influence and nourish the development and spread of the tumour. While initially quite promising, OV therapy has been met with a myriad of barriers due to the unwelcoming nature of the TME. Riddled with immunosuppressive factors and physical barriers, many tumours have proven impenetrable by OVs. Herein, we review the diverse array of approaches being used to target each component of the TME from enhancing entry into specific tumour types, breaking through the dense tumour stroma, eliminating cancer stem cells, and activating the immune system. We highlight the value of combination approaches which have led to complete successes in several in vivo models, some of which have entered clinical development. |
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| Keywords: | Oncolytic virus Tumour microenvironment Targeted therapy Combination Therapies |
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