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Oncolytic Viruses

Diagram of tumor cell destruction caused by Oncolytic Viruses

Oncolytic viruses may target and replicate within tumor cells, leading to tumor cell destruction and activation of cytotoxic T cells.

  • Oncolytic viruses are naturally occurring or genetically engineered viruses that preferentially target and replicate within tumor cells, leading to tumor cell destruction1-3
  • Tumor cells often have altered molecular mechanisms that favor viral replication, making them uniquely susceptible to viral infection and propagation3
    • Infection is initiated when oncolytic viruses attach to specific, highly expressed receptors on tumor cells2
    • Once internalized, they replicate and produce viral proteins, the process of which leads to host tumor cell lysis or death, releasing tumor antigens and new viruses into the tumor microenvironment1,2,4
  • Similar to immune signaling pathways, viral infection can influence the antitumor immune response5
    • Oncolytic viruses can be either “unarmed” or “armed” and can activate an antitumor immune response, in part by promoting tumor inflammation:
      • Unarmed oncolytic viruses lyse host cells, releasing tumor antigens that prime and activate cytotoxic T cells to infiltrate and eliminate the tumor2,4
      • In addition to lysing host cells, armed oncolytic viruses are engineered to initiate expression of immunomodulatory proteins in tumor cells, which may further activate the antitumor immune response4,6-8

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REFERENCES–Oncolytic viruses

1. Babiker HM, Riaz IB, Husnain M, Borad MJ. Oncolytic virotherapy including Rigvir and standard therapies in malignant melanoma. Oncolytic Virother. 2017;6:11-18. 2. Kaufman HL, Kohlhapp FJ, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nat Rev Drug Discov. 2015;14(9):642-662. 3. Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy: a new era of cancer treatment at dawn. Cancer Sci. 2016;107(10):1373-1379. 4. Seymour LW, Fisher KD. Oncolytic viruses: finally delivering. Br J Cancer. 2016;114(4):357-361. 5. Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321-330. 6. Aurelian L. Oncolytic viruses as immunotherapy: progress and remaining challenges. Onco Targets Ther. 2016;9:2627-2637. 7. Uusi-Kerttula H, Hulin-Curtis S, Davies J, Parker AL. Oncolytic adenovirus: strategies and insights for vector design and immuno-oncolytic applications. Viruses. 2015;7(11):6009-6042. 8. Tysome JR, Lemoine NR, Wang Y. Update on oncolytic viral therapy - targeting angiogenesis. Onco Targets Ther. 2013;6:1031-1040. 9. Zamarin D, Holmgaard RB, Subudhi SK, et al. Localized oncolytic virotherapy overcomes systemic tumor resistance to immune checkpoint blockade immunotherapy. Sci Transl Med. 2014;6(226):226ra32. doi:10.1124/scitranslmed.3008095. 10. Li X, Wang P, Li H, et al. The efficacy of oncolytic adenovirus is mediated by T-cell responses against virus and tumor in Syrian hamster model. Clin Cancer Res. 2017;23(1):239-249. 11. Tuve S, Liu Y, Tragoolpua K, et al. In situ adenovirus vaccination engages T effector cells against cancer. Vaccine. 2009;27(31):4225-4239. 12. Kim HS, Kim-Schulze S, Kim DW, Kaufman HL. Host lymphodepletion enhances the therapeutic activity of an oncolytic vaccinia virus expressing 4-1BB ligand. Cancer Res. 2009;69(21):8516-8525. 13. Chen CY, Wang PY, Hutzen B, et al. Cooperation of oncolytic herpes virotherapy and PD-1 blockade in murine rhabdomyosarcoma models. Sci Rep. 2017;7(1):2396. doi:10.1038/s41598-017-02503-8. 14. Chen C-Y, Hutzen B, Wedekind MF, Cripe TP. Oncolytic virus and PD-1/PD-L1 blockade combination therapy. Oncolytic Virother. 2018;7:65-77.