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Cancer Treatment and Research... 2022Today, the pancreatic cancer prognosis is poor and genetic technology is developing to treat various types of cancers. Scientists are actively looking for a new... (Review)
Review
BACKGROUND
Today, the pancreatic cancer prognosis is poor and genetic technology is developing to treat various types of cancers. Scientists are actively looking for a new technique to design a therapeutic strategy to treat pancreatic cancer. Several oncolytic viruses are known to be valuable tools for pancreatic cancer treatment. Recent Studies demonstrate their effectiveness and safety in various administration routes such as direct intratumoral, intracutaneous, intravascular, and other routes.
METHOD
In this study, all studies conducted in the past 20 years have been reviewed. Reputable scientific databases including Irandoc, Scopus, Google Scholar and PubMed, are searched for the keywords of Pancreatic cancer, oncolytic, viruses and treatment and the latest information about them is obtained.
RESULTS
Engineering the oncolytic viruses' genome and insertion of intended transgenes including cytokines or shRNAs, has caused promising promotions in pancreatic cancer treatment. Some oncolytic viruses inhibit tumors directly and some through activation of immune responses.
CONCLUSION
This approach showed some signs of success in efficiency like immune system activation in the tumor environment, effective virus targeting in the tumor cells by systemic administration, and enhanced patient survival in comparison with the control group. But of course, until now, using these oncolytic viruses alone has not been effective in elimination of tumors.
Topics: Humans; Oncolytic Virotherapy; Oncolytic Viruses; Pancreatic Neoplasms
PubMed: 35460973
DOI: 10.1016/j.ctarc.2022.100563 -
Current Opinion in Immunology Apr 2018Initially, direct oncolysis was thought to be the sole mechanism through which oncolytic viruses (OVs) exert their anti-tumor effect, and the immune system was perceived... (Review)
Review
Initially, direct oncolysis was thought to be the sole mechanism through which oncolytic viruses (OVs) exert their anti-tumor effect, and the immune system was perceived as the major obstacle in oncolytic virotherapy. Over the last decade, there has been a lot of debate on whether the immune system is a friend or foe of OVs. However, we are now at a stage where the initial thinking has been reversed as a result of compelling evidence that the immune system plays a critical role in the success of oncolytic virotherapy. In this review we discuss the importance of the involvement of innate and adaptive immunity for therapeutic efficacy of OVs, and the rational combination of OVs with other immunotherapies for further enhancement of overall therapeutic outcome.
Topics: Adaptive Immunity; Animals; Cell Death; Combined Modality Therapy; Genetic Vectors; Humans; Immunity; Immunomodulation; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 29550660
DOI: 10.1016/j.coi.2018.03.008 -
Viruses Sep 2023Oncolytic viruses offer a promising approach to tumor treatment. These viruses not only have a direct lytic effect on tumor cells but can also modify the tumor... (Review)
Review
Oncolytic viruses offer a promising approach to tumor treatment. These viruses not only have a direct lytic effect on tumor cells but can also modify the tumor microenvironment and activate antitumor immunity. Due to their high pathogenicity, flaviviruses have often been overlooked as potential antitumor agents. However, with recent advancements in genetic engineering techniques, an extensive history with vaccine strains, and the development of new attenuated vaccine strains, there has been a renewed interest in the Flavivirus genus. Flaviviruses can be genetically modified to express transgenes at acceptable levels, and the stability of such constructs has been greatly improving over the years. The key advantages of flaviviruses include their reproduction cycle occurring entirely within the cytoplasm (avoiding genome integration) and their ability to cross the blood-brain barrier, facilitating the systemic delivery of oncolytics against brain tumors. So far, the direct lytic effects and immunomodulatory activities of many flaviviruses have been widely studied in experimental animal models across various types of tumors. In this review, we delve into the findings of these studies and contemplate the promising potential of flaviviruses in oncolytic therapies.
Topics: Animals; Flavivirus; Oncolytic Virotherapy; Oncolytic Viruses; Brain Neoplasms; Genetic Engineering; Tumor Microenvironment
PubMed: 37896752
DOI: 10.3390/v15101973 -
Seminars in Cancer Biology Nov 2022The intentional use of viruses for cancer therapy dates back over a century. As viruses are inherently immunogenic and naturally optimized delivery vehicles, repurposing... (Review)
Review
The intentional use of viruses for cancer therapy dates back over a century. As viruses are inherently immunogenic and naturally optimized delivery vehicles, repurposing viruses for drug delivery, tumor antigen presentation, or selective replication in cancer cells represents a simple and elegant approach to cancer treatment. While early virotherapy was fraught with harsh side effects and low response rates, virus-based therapies have recently seen a resurgence due to newfound abilities to engineer and tune oncolytic viruses, virus-like particles, and virus-mimicking nanoparticles for improved safety and efficacy. However, despite their great potential, very few virus-based therapies have made it through clinical trials. In this review, we present an overview of virus-inspired approaches for cancer therapy, discuss engineering strategies to enhance their mechanisms of action, and highlight their application for overcoming the challenges of traditional cancer therapies.
Topics: Humans; Oncolytic Viruses; Oncolytic Virotherapy; Immunotherapy; Neoplasms; Nanoparticles
PubMed: 34182141
DOI: 10.1016/j.semcancer.2021.06.021 -
Nature Communications Jan 2024Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are...
Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are associated with cancer progression, yet their formation mechanism and role in oncolytic virotherapy remain elusive. In this study, we demonstrate that, in glioma, upregulation of IGF2BP3 enhances the expression of E3 ubiquitin protein ligase MIB1, promoting FTO degradation via the ubiquitin-proteasome pathway. This results in increased m6A-mediated CSF3 release and NET formation. Oncolytic herpes simplex virus (oHSV) stimulates IGF2BP3-induced NET formation in malignant glioma. In glioma models in female mice, a BET inhibitor enhances the oncolytic activity of oHSV by impeding IGF2BP3-induced NETosis, reinforcing virus replication through BRD4 recruitment with the CDK9/RPB-1 complex to HSV gene promoters. Our findings unveil the regulation of m6A-mediated NET formation, highlight oncolytic virus-induced NETosis as a critical checkpoint hindering oncolytic potential, and propose targeting NETosis as a strategy to overcome resistance in oncolytic virotherapy.
Topics: Female; Mice; Animals; Oncolytic Virotherapy; Drug Resistance, Neoplasm; Nuclear Proteins; Transcription Factors; Glioma; Simplexvirus; Oncolytic Viruses
PubMed: 38167409
DOI: 10.1038/s41467-023-44576-2 -
Viruses Jan 2023In the 1990s, adenovirus became one of the first virus types to be genetically engineered to selectively destroy cancer cells. In the intervening years, the field of... (Review)
Review
In the 1990s, adenovirus became one of the first virus types to be genetically engineered to selectively destroy cancer cells. In the intervening years, the field of "oncolytic viruses" has slowly progressed and culminated in 2015 with the FDA approval of Talimogene laherparepvec, a genetically engineered herpesvirus, for the treatment of metastatic melanoma. Despite the slower progress in translating oncolytic adenovirus to the clinic, interest in the virus remains strong. Among all the clinical trials currently using viral oncolytic agents, the largest proportion of these are using recombinant adenovirus. Many trials are currently underway to use oncolytic virus in combination with immune checkpoint inhibitors (ICIs), and early results using oncolytic adenovirus in this manner are starting to show promise. Many of the existing strategies to engineer adenoviruses were designed to enhance selective tumor cell replication without much regard to interactions with the immune system. Adenovirus possesses a wide range of viral factors to attenuate both innate anti-viral pathways and immune cell killing. In this review, we summarize the strategies of oncolytic adenoviruses currently in clinical trials, and speculate how the mutational backgrounds of these viruses may impact upon the efficacy of these agents in oncolytic and immunotherapy. Despite decades of research on human adenoviruses, the interactions that these viruses have with the immune system remains one of the most understudied aspects of the virus and needs to be improved to rationally design the next generation of engineered viruses.
Topics: Humans; Adenoviridae; Melanoma; Oncolytic Virotherapy; Adenoviruses, Human; Oncolytic Viruses
PubMed: 36851572
DOI: 10.3390/v15020358 -
Cytokine & Growth Factor Reviews Dec 2020Tumors represent a hostile environment for the effector cells of cancer immunosurveillance. Immunosuppressive receptors and soluble or membrane-bound ligands are... (Review)
Review
Tumors represent a hostile environment for the effector cells of cancer immunosurveillance. Immunosuppressive receptors and soluble or membrane-bound ligands are abundantly exposed and released by malignant entities and their stromal accomplices. As a consequence, executioners of antitumor immunity inefficiently navigate across cancer tissues and fail to eliminate malignant targets. By inducing immunogenic cancer cell death, oncolytic viruses profoundly reshape the tumor microenvironment. They trigger the local spread of danger signals and tumor-associated (as well as viral) antigens, thus attracting antigen-presenting cells, promoting the activation and expansion of lymphocytic populations, facilitating their infiltration in the tumor bed, and reinvigorating cytotoxic immune activity. The present review recapitulates key chemokines, growth factors and other cytokines that orchestrate this ballet of antitumoral leukocytes upon oncolytic virotherapy.
Topics: Cytokines; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 33183957
DOI: 10.1016/j.cytogfr.2020.10.007 -
British Journal of Cancer Feb 2016Oncolytic viruses can be found at the confluence of virology, genetic engineering and pharmacology where versatile platforms for molecularly targeted anticancer agents... (Review)
Review
Oncolytic viruses can be found at the confluence of virology, genetic engineering and pharmacology where versatile platforms for molecularly targeted anticancer agents can be designed and optimised. Oncolytic viruses offer several important advantages over traditional approaches, including the following. (1) Amplification of the active agent (infectious virus particles) within the tumour. This avoids unnecessary exposure to normal tissues experienced during delivery of traditional stoichiometric chemotherapy and maximises the therapeutic index. (2) The active cell-killing mechanisms, often independent of programmed death mechanisms, should decrease the emergence of acquired drug resistance. (3) Lytic death of cancer cells provides a pro-inflammatory microenvironment and the potential for induction of an anticancer vaccine response. (4) Tumour-selective expression and secretion of encoded anticancer biologics, providing a new realm of potent and cost-effective-targeted therapeutics.
Topics: Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 26766734
DOI: 10.1038/bjc.2015.481 -
The Journal of Clinical Investigation Mar 2019Oncolytic virotherapy (OVT) is a promising approach in which WT or engineered viruses selectively replicate and destroy tumor cells while sparing normal ones. In the... (Review)
Review
Oncolytic virotherapy (OVT) is a promising approach in which WT or engineered viruses selectively replicate and destroy tumor cells while sparing normal ones. In the last two decades, different oncolytic viruses (OVs) have been modified and tested in a number of preclinical studies, some of which have led to clinical trials in cancer patients. These clinical trials have revealed several critical limitations with regard to viral delivery, spread, resistance, and antiviral immunity. Here, we focus on promising research strategies that have been developed to overcome the aforementioned obstacles. Such strategies include engineering OVs to target a broad spectrum of tumor cells while evading the immune system, developing unique delivery mechanisms, combining other immunotherapeutic agents with OVT, and using clinically translatable mouse tumor models to potentially translate OVT more readily into clinical settings.
Topics: Animals; Humans; Mice; Neoplasms, Experimental; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 30829653
DOI: 10.1172/JCI122287 -
Frontiers in Immunology 2023Oncolytic virotherapy (OVT) is a promising form of cancer treatment that uses genetically engineered viruses to replicate within cancer cells and trigger anti-tumor... (Review)
Review
Oncolytic virotherapy (OVT) is a promising form of cancer treatment that uses genetically engineered viruses to replicate within cancer cells and trigger anti-tumor immune response. In addition to killing cancer cells, oncolytic viruses can also remodel the tumor microenvironment and stimulate a long-term anti-tumor immune response. Despite achieving positive results in cellular and organismal studies, there are currently only a few approved oncolytic viruses for clinical use. Vaccinia virus (VACV) has emerged as a potential candidate due to its ability to infect a wide range of cancer cells. This review discusses the mechanisms, benefits, and clinical trials of oncolytic VACVs. The safety and efficacy of different viral backbones are explored, as well as the effects of oncolytic VACVs on the tumor microenvironment. The potential combination of oncolytic VACVs with immunotherapy or traditional therapies is also highlighted. The review concludes by addressing prospects and challenges in the field of oncolytic VACVs, with the aim of promoting further research and application in cancer therapy.
Topics: Humans; Oncolytic Viruses; Vaccinia virus; Oncolytic Virotherapy; Immunotherapy; Neoplasms; Tumor Microenvironment
PubMed: 38283361
DOI: 10.3389/fimmu.2023.1324744