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      Oncolytic viruses: A novel treatment strategy for breast cancer

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          Abstract

          Breast cancer, an unceasingly occurring neoplasm, is one of the major determinants of mortality in women. Several ineffective attempts have been pursued using with conventional therapies against breast cancer. Resistance to existing therapies and their respective debilitating adverse effects have led research toward a new era of cancer treatment using viruses. Virotherapy constitutes a developing treatment modality with multiple mechanisms of therapeutic activity in which the viruses can be directly oncolyticand can express transgenes or induce host immune response against tumor cells. Several different DNA- and RNA-containing viruses have been considered for virotherapy of breast cancer including adenovirus, herpes virus, vaccinia, reovirus, Newcastle Disease virus, measles virus and vesicular stomatitis virus. This review aims to summarize the viro-therapeutical agents against breast malignancies. Key Scientific Concepts of Review: In this review paper, we proposed a new strategy to virus's combinatorial treatments using several kinds of transgenes and drugs. These recombinant viruses have provided evidence of treatment efficacy against human breast cancer.

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          A phase I study of OncoVEXGM-CSF, a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor.

          To conduct a phase I clinical trial with a second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEXGM-CSF) to determine the safety profile of the virus, look for evidence of biological activity, and identify a dosing schedule for later studies. The virus was administered by intratumoral injection in patients with cutaneous or s.c. deposits of breast, head and neck and gastrointestinal cancers, and malignant melanoma who had failed prior therapy. Thirteen patients were in a single-dose group, where doses of 10(6), 10(7), and 10(8) plaque-forming units (pfu)/mL were tested, and 17 patients were in a multidose group testing a number of dose regimens. The virus was generally well tolerated with local inflammation, erythema, and febrile responses being the main side effects. The local reaction to injection was dose limiting in HSV-seronegative patients at 10(7) pfu/mL. The multidosing phase thus tested seroconverting HSV-seronegative patients with 10(6) pfu/mL followed by multiple higher doses (up to 10(8) pfu/mL), which was well tolerated by all patients. Biological activity (virus replication, local reactions, granulocyte macrophage colony-stimulating factor expression, and HSV antigen-associated tumor necrosis), was observed. The duration of local reactions and virus replication suggested that dosing every 2 to 3 weeks was appropriate. Nineteen of 26 patient posttreatment biopsies contained residual tumor of which 14 showed tumor necrosis, which in some cases was extensive, or apoptosis. In all cases, areas of necrosis also strongly stained for HSV. The overall responses to treatment were that three patients had stable disease, six patients had tumors flattened (injected and/or uninjected lesions), and four patients showed inflammation of uninjected as well as the injected tumor, which, in nearly all cases, became inflamed. Onco VEXGM-CSF is well tolerated and can be safely administered using the multidosing protocol described. Evidence of an antitumor effect was seen.
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            Oncolytic virus therapy: A new era of cancer treatment at dawn

            Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T‐Vec (talimogene laherparepvec), a second‐generation oncolytic herpes simplex virus type 1 (HSV‐1) armed with GM‐CSF, was recently approved as the first oncolytic virus drug in the USA and Europe. The phase III trial proved that local intralesional injections with T‐Vec in advanced malignant melanoma patients can not only suppress the growth of injected tumors but also act systemically and prolong overall survival. Other oncolytic viruses that are closing in on drug approval in North America and Europe include vaccinia virus JX‐594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM‐CSF‐expressing adenovirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild‐type variant of reovirus, for head and neck cancer. In Japan, a phase II clinical trial of G47∆, a third‐generation oncolytic HSV‐1, is ongoing in glioblastoma patients. G47∆ was recently designated as a “Sakigake” breakthrough therapy drug in Japan. This new system by the Japanese government should provide G47∆ with priority reviews and a fast‐track drug approval by the regulatory authorities. Whereas numerous oncolytic viruses have been subjected to clinical trials, the common feature that is expected to play a major role in prolonging the survival of cancer patients is an induction of specific antitumor immunity in the course of tumor‐specific viral replication. It appears that it will not be long before oncolytic virus therapy becomes a standard therapeutic option for all cancer patients.
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              Into the clinic: Talimogene laherparepvec (T-VEC), a first-in-class intratumoral oncolytic viral therapy

              With the recent regulatory approval of Talimogene laherparepvec (T-VEC) for the treatment of advanced of melanoma in the United States, Europe and Australia, oncolytic virus immunotherapy has earned its place in the clinic. However, the adoption of T-VEC by the U.S. oncology community has been slow, and so far has been largely limited to specialized cancer centers. Limiting factors include the intratumoral route of administration, which is unfamiliar to medical oncologists, biosafety concerns related to the use of a live virus in the clinic, and the explosion of other therapeutic strategies now available for the treatment of advanced melanoma. Herein, we review the development of T-VEC, and suggest how it fits into the in the current clinical treatment paradigm, and provide pearls for drug preparation, administration, and monitoring of response to therapy.
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                Author and article information

                Contributors
                Journal
                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                2352-4820
                2352-3042
                16 December 2021
                March 2023
                16 December 2021
                : 10
                : 2
                : 430-446
                Affiliations
                [a ]Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran 1435916471, Iran
                [b ]Mehrestan Health Network, Iranshahr University of Medical Sciences, Iranshahr 9966118984, Iran
                [c ]University of Trieste, Department of Medical, Surgical & Health Sciences, Trieste 34128, Italy
                [d ]University Health Agency Giuliano-Isontina (ASUGI), Public Health Department, Trieste, Italy
                [e ]Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz 5167956561, Iran
                [f ]Shahid Akbarabadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences (IUMS), Tehran 1997673144, Iran
                [g ]Department of General Surgery, Urmia University of Medical Science, Urmia 57147, Iran
                [h ]Department of Pediatrics, Iran University of Medical Sciences, Tehran 1449614535, Iran
                [i ]JC School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong Special Administrative Region 999077, China
                [j ]Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran 169875931, Iran
                [k ]Health Research Center, Baqiyatallah University of Medical Sciences, Tehran 1435916471, Iran
                [l ]Razi Vaccine and Serum Research Institute, Agriculture Research, Education and Extension Organization (AREEO), Karaj 11365-1558, Iran
                [m ]Department of Neurosurgery, University Medical Center, Tuebingen 72076, Germany
                Author notes
                []Corresponding author. mhmjvbt81@ 123456gmail.com
                [∗∗ ]Corresponding author. sanaz_th91@ 123456yahoo.com
                Article
                S2352-3042(21)00161-6
                10.1016/j.gendis.2021.11.011
                10201557
                b84a8d38-0870-440a-8c8b-a0fa549065eb
                © 2021 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 30 July 2021
                : 27 September 2021
                : 19 November 2021
                Categories
                Review Article

                adenovirus,breast cancer,herpes virus,measles virus,newcastle disease virus,reovirus,vaccinia,vesicular stomatitis virus,virotherapy

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