Oncolytic Immunotherapy: Can’t Start a Fire Without a Spark |
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| Institution: | 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 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. 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;1. Department of Urology, University of California San Diego, 9400 Campus Point Drive, MC7987, La Jolla, CA 92093, USA;2. Division of Hematology-Oncology, Department of Internal Medicine, University of California San Diego, La Jolla, CA 92093, USA;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 |
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| Abstract: | Recent advances in cancer immunotherapy have renewed interest in oncolytic viruses (OVs) as a synergistic platform for the development of novel antitumor strategies. Cancer cells adopt multiple mechanisms to evade and suppress antitumor immune responses, essentially establishing a non-immunogenic (‘cold’) tumor microenvironment (TME), with poor T-cell infiltration and low mutational burden. Limitations to the efficacy of immunotherapy still exist, especially for a variety of solid tumors, where new approaches are necessary to overcome physical barriers in the TME and to mitigate adverse effects associated with current immunotherapeutics. OVs offer an attractive alternative by inducing direct oncolysis, immunogenic cell death, and immune stimulation. These multimodal mechanisms make OVs well suited to reprogram non-immunogenic tumors and TME into inflamed, immunogenic (‘hot’) tumors; enhanced release of tumor antigens by dying cancer cells is expected to augment T-cell infiltration, thereby eliciting potent antitumor immunity. Advances in virus engineering and understanding of tumor biology have allowed the optimization of OV-tumor selectivity, oncolytic potency, and immune stimulation. However, OV antitumor activity is likely to achieve its greatest potential as part of combinatorial strategies with other immune or cancer therapeutics. |
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| Keywords: | Oncolytic virus Immunotherapy Cancer Immune checkpoint Tumor reprogramming |
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