Histone Deacetylase Inhibitors Enhance the Therapeutic Potential of Reovirus in Multiple Myeloma

Molecular Cancer Therapeutics
Andrew StiffFlavia Pichiorri

Abstract

Multiple myeloma remains incurable and the majority of patients die within 5 years of diagnosis. Reolysin, the infusible form of human reovirus (RV), is a novel viral oncolytic therapy associated with antitumor activity likely resulting from direct oncolysis and a virus-mediated antitumor immune response. Results from our phase I clinical trial investigating single agent Reolysin in patients with relapsed multiple myeloma confirmed tolerability, but no objective responses were evident, likely because the virus selectively entered the multiple myeloma cells but did not actively replicate. To date, the precise mechanisms underlying the RV infectious life cycle and its ability to induce oncolysis in patients with multiple myeloma remain unknown. Here, we report that junctional adhesion molecule 1 (JAM-1), the cellular receptor for RV, is epigenetically regulated in multiple myeloma cells. Treatment of multiple myeloma cells with clinically relevant histone deacetylase inhibitors (HDACi) results in increased JAM-1 expression as well as increased histone acetylation and RNA polymerase II recruitment to its promoter. Furthermore, our data indicate that the combination of Reolysin with HDACi, potentiates RV killing activity of multipl...Continue Reading

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Citations

Mar 28, 2018·Journal of Hematology & Oncology·Rosemarie Tremblay-LeMayHong Chang
Jul 3, 2019·Journal for Immunotherapy of Cancer·Louise M E MüllerFiona Errington-Mais
Mar 7, 2020·Cells·Cinnie Yentia SoekojoWee Joo Chng
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Dec 14, 2018·Oncoimmunology·Jonathan G PolLorenzo Galluzzi
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Aug 29, 2018·ACS Infectious Diseases·Michael PhanJean-Simon Diallo
Aug 26, 2021·Expert Review of Hematology·Ayesha SarwarFaiz Anwer

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