Oncolytic Herpes Simplex Virus-Based Therapies for Cancer

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Abstract

With the increased worldwide burden of cancer, including aggressive and resistant cancers, oncolytic virotherapy has emerged as a viable therapeutic option. Oncolytic herpes simplex virus (oHSV) can be genetically engineered to target cancer cells while sparing normal cells. This leads to the direct killing of cancer cells and the activation of the host immunity to recognize and attack the tumor. Different variants of oHSV have been developed to optimize its antitumor effects. In this review, we discuss the development of oHSV, its antitumor mechanism of action and the clinical trials that have employed oHSV variants to treat different types of tumor.

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STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors.

Seng-Ryong Woo, Mercedes Fuertes, Leticia Corrales … (2014)

Spontaneous T cell responses against tumors occur frequently and have prognostic value in patients. The mechanism of innate immune sensing of immunogenic tumors leading to adaptive T cell responses remains undefined, although type I interferons (IFNs) are implicated in this process. We found that spontaneous CD8(+) T cell priming against tumors was defective in mice lacking stimulator of interferon genes complex (STING), but not other innate signaling pathways, suggesting involvement of a cytosolic DNA sensing pathway. In vitro, IFN-? production and dendritic cell activation were triggered by tumor-cell-derived DNA, via cyclic-GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3). In the tumor microenvironment in vivo, tumor cell DNA was detected within host antigen-presenting cells, which correlated with STING pathway activation and IFN-? production. Our results demonstrate that a major mechanism for innate immune sensing of cancer occurs via the host STING pathway, with major implications for cancer immunotherapy. Copyright © 2014 Elsevier Inc. All rights reserved.

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Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.

Robert Andtbacka, Howard L. Kaufman, Frances A Collichio … (2015)

Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1-derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial.

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Oncolytic viruses: a new class of immunotherapy drugs

Howard L. Kaufman, Frederick Kohlhapp, Andrew Zloza (2015)

Key Points Oncolytic viruses mediate anti-tumour responses through a dual mechanism involving viral oncolysis of cancer cells and induction of host anti-tumour immunity. The molecular and cellular mechanisms of action are not fully elucidated but are likely to depend on viral replication within transformed cells, induction of primary cell death, interaction with tumour cell antiviral elements, release of danger signals and initiation of innate and adaptive anti-tumour immunity. A variety of native and genetically modified viruses have been utilized as oncolytic vectors in preclinical studies, which have demonstrated therapeutic activity against several types of cancer. Oncolytic viruses can be genetically modified to decrease pathogenicity, increase lytic potential and enhance immunogenicity, improving the risk–benefit ratio for clinical development. The approval of a modified adenovirus, H101, in China and the pending approval of a modified herpes simplex virus type 1 (HSV-1) encoding granulocyte–macrophage colony stimulating factor (GM-CSF), termed talimogene laherparepvec (T-VEC), by the US Food and Drug Administration (FDA) in the United States is likely to promote further drug development within this new class of cancer therapeutics. Oncolytic viruses face unique challenges in drug development, including the need for optimal clinical trial designs and response assessment that capture therapeutic responses, different regulatory and commercialization pathways, the need for live culture scale-up procedures, and novel biosafety concerns related to viral persistence in patients and transmission to household contacts and health-care providers. Supplementary information The online version of this article (doi:10.1038/nrd4663) contains supplementary material, which is available to authorized users.

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Bernat Soria: Role: Academic Editor

Journal

Journal ID (nlm-ta): Cells

Journal ID (iso-abbrev): Cells

Journal ID (publisher-id): cells

Title: Cells

Publisher: MDPI

ISSN (Electronic): 2073-4409

Publication date (Electronic): 18 June 2021

Publication date Collection: June 2021

Volume: 10

Issue: 6

Electronic Location Identifier: 1541

Affiliations

[1 ]Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology, P.O. Box 6086, Riyadh 11451, Saudi Arabia; Naldrak@ 123456kacst.edu.sa (N.A.); smalsaab@ 123456kacst.edu.sa (S.A.); asalgethami@ 123456kacst.edu.sa (A.A.)

[2 ]National Center for Biotechnology, Life Science and Environmental Research Institute, King Abdulaziz City for Science and Technology, P.O. Box 6086, Riyadh 11451, Saudi Arabia

[3 ]Center for Stem Cell Therapeutics and Imaging (CSTI), Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA; DBHERE@ 123456BWH.HARVARD.EDU (D.B.); HWAKIMOTO@ 123456mgh.harvard.edu (H.W.); KSHAH@ 123456bwh.harvard.edu (K.S.)

[4 ]Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

[5 ]BWH Center of Excellence for Biomedicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA

[6 ]Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

[7 ]Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA

Author notes

[* ]Correspondence: malomary@ 123456kacst.edu.sa (M.N.A.); nzaidan@ 123456kacst.edu.sa (N.Z.)

Author information

Norah Aldrak https://orcid.org/0000-0002-6966-0395

Deepak Bhere https://orcid.org/0000-0003-4142-5518

Hiroaki Wakimoto https://orcid.org/0000-0001-8225-241X

Mohammad N. Alomary https://orcid.org/0000-0001-7909-4377

Nada Zaidan https://orcid.org/0000-0002-3358-9814

Article

Publisher ID: cells-10-01541

DOI: 10.3390/cells10061541

PMC ID: 8235327

PubMed ID: 34207386

SO-VID: ed50d102-7171-4bcc-afdf-30d95e69b86b

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

History

Date received : 13 April 2021

Date accepted : 26 May 2021

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Oncolytic Herpes Simplex Virus-Based Therapies for Cancer

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Cancer Immunotherapy

Most cited references 106

STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors.

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.

Oncolytic viruses: a new class of immunotherapy drugs

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