A rational relationship: Oncolytic virus vaccines as functional partners for adoptive T cell therapy |
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| Institution: | 1. SillaJen Biotherapeutics, 450 Sansome Street, Suite 650, San Francisco, CA 94111, United States;2. University of Southern California, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue #3440, Los Angeles, CA 90033, United States;3. Department of Molecular Medicine, Rochester, MN, United States;4. Mayo Clinic Cancer Center, Scottsdale, AZ, United States;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. Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Rome, Italy;2. Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands;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. 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 Medicine, Baylor College of Medicine, Houston, TX, USA;2. Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children’s Hospital, Houston Methodist Hospital, Houston, TX, USA;3. Department of Pathology, Baylor College of Medicine, Houston, TX, USA;4. Department of Otolaryngology, Baylor College of Medicine, Houston, TX, USA;5. Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN, USA;6. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA |
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| Abstract: | Tumours employ a variety of immune-evasion and suppression mechanisms to impair development of functional tumor-specific T cells and subvert T cell-mediated immunity in the tumour microenvironment. Adoptive T cell therapy (ACT) aims to overcome these barriers and overwhelm tumor defenses with a bolus of T cells that were selectively expanded ex vivo. Although this strategy has been effective in liquid tumors and melanomas, many tumors appear to be resistant to ACT. Several factors are thought to play into this resistance, including poor engraftment and persistence of transferred cells, tumour cell heterogeneity and antigen loss, poor immune cell recruitment and infiltration into the tumour, and susceptibility to local immunosuppression in the tumor microenvironment. Oncolytic viruses (OV) have been identified as powerful stimulators of the anti-tumour immune response. As such, OVs are inherently well-positioned to act in synergy with ACT to bolster the anti-tumour T cell response. Further, OV vaccines, wherein tumour-associated antigens are encoded into the viral backbone, have proven to be remarkable in boosting antigen-specific T cell response. Pre-clinical studies have revealed remarkable therapeutic outcomes when OV vaccines are paired with ACT. In this scenario, OV vaccines are thought to function in a “push and pull” manner, where push refers to expanding T cells in the periphery and pull refers to recruiting those cells into the tumour that has been rendered amenable to T cell attack by the actions of the OV. In this review, we discuss barriers that limit eradication of tumors by T cells, highlight attributes of OVs that break down these barriers and present strategies for rational combinations of ACT with OV vaccines. |
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| Keywords: | Oncolytic virus Adoptive cell therapy Cancer vaccines |
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