Histone deacetylase inhibitors enhance oncolytic herpes simplex virus therapy for malignant meningioma.

Autor: Kawamura Y; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Hua L; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China., Gurtner A; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Wong E; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Kiyokawa J; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Shah N; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Gorham J; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Wakimoto H; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Rabkin SD; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Martuza RL; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Wakimoto H; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: hwakimoto@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2022 Nov; Vol. 155, pp. 113843. Date of Electronic Publication: 2022 Oct 08.
DOI: 10.1016/j.biopha.2022.113843
Abstrakt: Approximately 20% of meningiomas are not benign (higher grade) and tend to relapse after surgery and radiation therapy. Malignant (anaplastic) meningioma (MM) is a minor subset of high-grade meningioma that is lethal with no effective treatment options currently. Oncolytic herpes simplex virus (oHSV) is a powerful anti-cancer modality that induces both direct cell death and anti-tumor immunity, and has shown activity in preclinical models of MM. However, clinically meaningful efficacy will likely entail rational mechanistic combination approaches. We here show that epigenome modulator histone deacetylase inhibitors (HDACi) increase anti-cancer effects of oHSV in human MM models, IOMM-Lee (NF2 wild-type) and CH157 (NF2 mutant). Minimally toxic, sub-micromolar concentrations of pan-HDACi, Trichostatin A and Panobinostat, substantively increased the infectability and spread of oHSV G47Δ within MM cells in vitro, resulting in enhanced oHSV-mediated killing of target cells when infected at low multiplicity of infection (MOI). Transcriptomics analysis identified selective alteration of mRNA processing and splicing modules that might underlie the potent anti-MM effects of combining HDACi and oHSV. In vivo, HDACi treatment increased intratumoral oHSV replication and boosted the capacity of oHSV to control the growth of human MM xenografts. Thus, our work supports further translational development of the combination approach employing HDACi and oHSV for the treatment of MM.
Competing Interests: Conflict of interest statement SDR and RLM are co-inventors on patents relating to oncolytic herpes simplex viruses, owned and managed by Georgetown University and Massachusetts General Hospital, which have received royalties from Amgen and ActiVec Inc. SDR acted as a consultant and received honoraria from Replimune, Cellinta, and Greenfire Bio, and honoraria and equity from EG 427. RLM. is on the S.A.B. and receives payment from Virogin Biotech Ltd.
(Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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