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      Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy

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          Abstract

          Background

          Oncolytic virotherapy (OVT) is a promising anti-tumor modality that utilizes oncolytic viruses (OVs) to preferentially attack cancers rather than normal tissues. With the understanding particularly in the characteristics of viruses and tumor cells, numerous innovative OVs have been engineered to conquer cancers, such as Talimogene Laherparepvec (T-VEC) and tasadenoturev (DNX-2401). However, the therapeutic safety and efficacy must be further optimized and balanced to ensure the superior safe and efficient OVT in clinics, and reasonable combination therapy strategies are also important challenges worthy to be explored.

          Main body

          Here we provided a critical review of the development history and status of OVT, emphasizing the mechanisms of enhancing both safety and efficacy. We propose that oncolytic virotherapy has evolved into the fourth generation as tumor immunotherapy. Particularly, to arouse T cells by designing OVs expressing bi-specific T cell activator (BiTA) is a promising strategy of killing two birds with one stone. Amazing combination of therapeutic strategies of OVs and immune cells confers immense potential for managing cancers. Moreover, the attractive preclinical OVT addressed recently, and the OVT in clinical trials were systematically reviewed.

          Conclusion

          OVs, which are advancing into clinical trials, are being envisioned as the frontier clinical anti-tumor agents coming soon.

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          Most cited references183

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          Cancer Statistics, 2021

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence. Incidence data (through 2017) were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2018) were collected by the National Center for Health Statistics. In 2021, 1,898,160 new cancer cases and 608,570 cancer deaths are projected to occur in the United States. After increasing for most of the 20th century, the cancer death rate has fallen continuously from its peak in 1991 through 2018, for a total decline of 31%, because of reductions in smoking and improvements in early detection and treatment. This translates to 3.2 million fewer cancer deaths than would have occurred if peak rates had persisted. Long-term declines in mortality for the 4 leading cancers have halted for prostate cancer and slowed for breast and colorectal cancers, but accelerated for lung cancer, which accounted for almost one-half of the total mortality decline from 2014 to 2018. The pace of the annual decline in lung cancer mortality doubled from 3.1% during 2009 through 2013 to 5.5% during 2014 through 2018 in men, from 1.8% to 4.4% in women, and from 2.4% to 5% overall. This trend coincides with steady declines in incidence (2.2%-2.3%) but rapid gains in survival specifically for nonsmall cell lung cancer (NSCLC). For example, NSCLC 2-year relative survival increased from 34% for persons diagnosed during 2009 through 2010 to 42% during 2015 through 2016, including absolute increases of 5% to 6% for every stage of diagnosis; survival for small cell lung cancer remained at 14% to 15%. Improved treatment accelerated progress against lung cancer and drove a record drop in overall cancer mortality, despite slowing momentum for other common cancers.
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            Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma.

            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 VIROTHERAPY

              Oncolytic virotherapy is an emerging treatment modality which uses replication competent viruses to destroy cancers. Advances in the past two years include preclinical proof of feasibility for a single-shot virotherapy cure, identification of drugs that accelerate intratumoral virus propagation, new strategies to maximize the immunotherapeutic potential of oncolytic virotherapy, and clinical confirmation of a critical viremic thereshold for vascular delivery and intratumoral virus replication. The primary clinical milestone was completion of accrual in a phase III trial of intratumoral herpes simplex virus therapy using talimogene laherparepvec for metastatic melanoma. Challenges for the field are to select ‘winners’ from a burgeoning number of oncolytic platforms and engineered derivatives, to transiently suppress but then unleash the power of the immune system to maximize both virus spread and anticancer immunity, to develop more meaningful preclinical virotherapy models and to manufacture viruses with orders of magnitude higher yields compared to established vaccine manufacturing processes.
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                Author and article information

                Contributors
                275379987@qq.com
                hongyi_xin@126.com
                hongwu_xin@126.com
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                25 July 2023
                25 July 2023
                2023
                : 21
                : 500
                Affiliations
                [1 ]GRID grid.410654.2, ISNI 0000 0000 8880 6009, Department of Biochemistry and Molecular Biology, Health Science Center, , Yangtze University, ; Jingzhou, 434023 Hubei China
                [2 ]GRID grid.410654.2, ISNI 0000 0000 8880 6009, College of Arts and Sciences, , Yangtze University, ; Jingzhou, 434023 Hubei China
                [3 ]GRID grid.410654.2, ISNI 0000 0000 8880 6009, The Second School of Clinical Medicine, , Yangtze University, ; Jingzhou, 434023 Hubei China
                [4 ]GRID grid.413247.7, ISNI 0000 0004 1808 0969, Xinzhou Traditional Chinese Medicine Hospital, , Zhongnan Hospital of Wuhan University (Xinzhou), ; Wuhan, 430000 Hubei China
                [5 ]GRID grid.410612.0, ISNI 0000 0004 0604 6392, School of Graduate Students, , Inner Mongolia Medical University, ; Inner Mongolian Autonomous Region, Hohhot, 010110 China
                [6 ]GRID grid.411609.b, ISNI 0000 0004 1758 4735, Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, , National Center for Children’s Health, ; Beijing, 100045 China
                [7 ]The Doctoral Scientific Research Center, People’s Hospital of Lianjiang, Guangdong, 524400 China
                [8 ]GRID grid.410560.6, ISNI 0000 0004 1760 3078, The Doctoral Scientific Research Center, Affiliated People’s Hospital of Lianjiang, , Guangdong Medical University, ; Guangdong, 524400 China
                Author information
                http://orcid.org/0000-0002-2112-1608
                Article
                4360
                10.1186/s12967-023-04360-8
                10369732
                37491263
                78076cfc-7fc7-4b08-9d5f-ada78c2a5034
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 28 December 2022
                : 16 July 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 31700736
                Award ID: 81872412
                Award Recipient :
                Funded by: The Central Government guides local funds for scientific and Technological Development (
                Award ID: XZ202201YD0024C
                Award Recipient :
                Funded by: Key R & D Program of Hubei Province
                Award ID: 2021BGD010
                Award Recipient :
                Funded by: Hubei Province Scientific and Technological Research Project
                Award ID: D20201306
                Award Recipient :
                Categories
                Review
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                © BioMed Central Ltd., part of Springer Nature 2023

                Medicine
                oncolytic virotherapy (ovt),oncolytic viruses (ovs),cancer,t-vec,bita
                Medicine
                oncolytic virotherapy (ovt), oncolytic viruses (ovs), cancer, t-vec, bita

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