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Advanced Materials (Deerfield Beach,... Mar 2023Immune checkpoint blockade (ICB) therapy shows excellent efficacy against malignancies; however, insufficient tumor immunogenicity and the immunosuppressive tumor...
Immune checkpoint blockade (ICB) therapy shows excellent efficacy against malignancies; however, insufficient tumor immunogenicity and the immunosuppressive tumor microenvironment (TME) are considered as the two major stumbling blocks to a broad ICB response. Here, a combinational therapeutic strategy is reported, wherein TME-reactive oxygen species/pH dual-responsive signal transducers and activators of transcription 3 inhibitor nanoprodrugs MPNPs are combined with oncolytic herpes simplex virus 1 virotherapy to synergistically ignite pyroptosis for enhancing immunotherapy. MPNPs exhibit a certain level of tumor accumulation, reduce tumor cell stemness, and enhance antitumor immune responses. Furthermore, the simultaneous application of oncolytic viruses (OVs) confers MPNPs with higher tumor penetration capacity and remarkable gasdermin-E-mediated pyroptosis, thereby reshaping the TME and transforming "cold" tumors into "hot" ones. This "fire of immunity" strategy successfully activates robust T-cell-dependent antitumor responses, potentiating ICB effects against local recurrence and pulmonary metastasis in preclinical "cold" murine triple-negative breast cancer and syngeneic oral cancer models. Collectively, this work may pave a new way and offer an unprecedented opportunity for the combination of OVs with nanomedicine for cancer immunotherapy.
Topics: Humans; Mice; Animals; Oncolytic Viruses; Pyroptosis; Oncolytic Virotherapy; Neoplasms; Immunotherapy; Immunity; Tumor Microenvironment; STAT3 Transcription Factor
PubMed: 36545949
DOI: 10.1002/adma.202209379 -
Journal For Immunotherapy of Cancer Dec 2023Whither oncolytic viruses? From the peak of their popularity in the early 2000s, when the ONYX-015 adenovirus had just entered the clinic, and then again in 2015 when...
Whither oncolytic viruses? From the peak of their popularity in the early 2000s, when the ONYX-015 adenovirus had just entered the clinic, and then again in 2015 when the Food and Drug Administration-approved talimogene laherparepvec (also known as OncoVEX), which briefly revived interest, oncolytic viruses (OVs) have mostly fallen out of favor despite the many pharmaceutical companies with OVs in development.This commentary enumerates and addresses the core conceptions, perceptions, and misconceptions that characterize the current 'trough of disillusionment' in which the field of anticancer virotherapy finds itself and suggests reasons for optimism.
Topics: United States; Humans; Oncolytic Viruses; Melanoma; Oncolytic Virotherapy
PubMed: 38135348
DOI: 10.1136/jitc-2023-007905 -
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 -
Critical Reviews in Oncology/hematology May 2023Oncolytic viruses (OV) are an attractive prospect due to their dual attack mechanism of direct cell lysis and potentiation of an antitumor immune response. Various... (Review)
Review
Oncolytic viruses (OV) are an attractive prospect due to their dual attack mechanism of direct cell lysis and potentiation of an antitumor immune response. Various oncolytic viral vectors are used in oncotherapy clinical trials, and one of their main problems is elimination by the reticuloendothelial system during systemic delivery. Nanoparticles (NPs) have received much attention in clinical trials due to their unique appearance characteristics, but they have created challenges due to the non-specificity of drug delivery to the target tissue and its elimination in blood circulation. In this regard, to increase the efficiency of nanoparticles in drug delivery, various chemical modifications can be applied to the surface of nanoparticles. To improve the performance of these two treatment options, the complex strategy of OVs encapsulated with nanoparticles can be used, which has brought successful clinical results in the treatment of various cancers. Here we will review each of the treatment methods and their functional mechanism.
Topics: Humans; Oncolytic Viruses; Oncolytic Virotherapy; Neoplasms; Drug Delivery Systems
PubMed: 37001838
DOI: 10.1016/j.critrevonc.2023.103980 -
Frontiers in Cellular and Infection... 2023Recent reports have revealed that oncolytic viruses (OVs) play a significant role in cancer therapy. The infection of OVs such as oncolytic vaccinia virus (OVV),... (Review)
Review
Recent reports have revealed that oncolytic viruses (OVs) play a significant role in cancer therapy. The infection of OVs such as oncolytic vaccinia virus (OVV), vesicular stomatitis virus (VSV), parvovirus, mammalian reovirus (MRV), human adenovirus, Newcastle disease virus (NDV), herpes simplex virus (HSV), avian reovirus (ARV), Orf virus (ORFV), inactivated Sendai virus (ISV), enterovirus, and coxsackievirus offer unique opportunities in immunotherapy through diverse and dynamic pathways. This mini-review focuses on the mechanisms of OVs-mediated virotherapy and their effects on immunogenic cell death (ICD), apoptosis, autophagy and regulation of the immune system.
Topics: Animals; Humans; Oncolytic Viruses; Immunogenic Cell Death; Neoplasms; Apoptosis; Immunity; Autophagy; Mammals
PubMed: 37009515
DOI: 10.3389/fcimb.2023.1142172 -
Advances in Experimental Medicine and... 2020Osteosarcoma remains an unmet medical need. Oncolytic viruses are gaining traction as novel cancer therapeutics. These viruses are either naturally nonpathogenic or... (Review)
Review
Osteosarcoma remains an unmet medical need. Oncolytic viruses are gaining traction as novel cancer therapeutics. These viruses are either naturally nonpathogenic or engineered to be safe by specific genetic deletions yet retain the ability to infect and kill human cancer cells and elicit anticancer immunity. Some versions are being specifically designed and tested in patients with osteosarcoma, though due to their generalized mechanism of action most are being tested in patients across a broad range of cancer types. The activity of these viruses is impacted not only by the susceptibility of tumor cells to infection but also by the tumor microenvironment (TME) and by tumor immunogenicity. Here we review the field of oncolytic viruses with a particular emphasis on highlighting any available data in preclinical osteosarcoma models or in patients with osteosarcoma. While in general the viruses have been shown safe to administer to patients by a variety of routes, their therapeutic efficacy to date has been limited. Given the low rate of adverse events and the likely absence of long-term side effects, the utility of oncolytic viruses will most likely be realized when used in combination with other agents.
Topics: Bone Neoplasms; Humans; Oncolytic Virotherapy; Oncolytic Viruses; Osteosarcoma; Tumor Microenvironment
PubMed: 32767235
DOI: 10.1007/978-3-030-43085-6_5 -
Nature Communications Jun 2023Oncolytic viruses (OVs) represent a type of encouraging multi-mechanistic drug for the treatment of cancer. However, attenuation of virulence, which is generally...
Oncolytic viruses (OVs) represent a type of encouraging multi-mechanistic drug for the treatment of cancer. However, attenuation of virulence, which is generally required for the development of OVs based on pathogenic viral backbones, is frequently accompanied by a compromised killing effect on tumor cells. By exploiting the property of viruses to evolve and adapt in cancer cells, we perform directed natural evolution on refractory colorectal cancer cell HCT-116 and generate a next-generation oncolytic virus M1 (NGOVM) with an increase in the oncolytic effect of up to 9690-fold. The NGOVM has a broader antitumor spectrum and a more robust oncolytic effect in a range of solid tumors. Mechanistically, two critical mutations are identified in the E2 and nsP3 genes, which accelerate the entry of M1 virus by increasing its binding to the Mxra8 receptor and antagonize antiviral responses by inhibiting the activation of PKR and STAT1 in tumor cells, respectively. Importantly, the NGOVM is well tolerated in both rodents and nonhuman primates. This study implies that directed natural evolution is a generalizable approach for developing next-generation OVs with an expanded scope of application and high safety.
Topics: Animals; Oncolytic Viruses; Oncolytic Virotherapy; Neoplasms
PubMed: 37296165
DOI: 10.1038/s41467-023-39156-3 -
International Journal of Molecular... Oct 2020Glioma tumors are one of the most devastating cancer types. Glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to... (Review)
Review
Glioma tumors are one of the most devastating cancer types. Glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advances in oncolytic immunotherapy have generated great expectations in the cancer therapy field. The use of oncolytic viruses (OVs) in cancer treatment is one such immune-related therapeutic alternative. OVs have a double oncolytic action by both directly destroying the cancer cells and stimulating a tumor specific immune response to return the ability of tumors to escape the control of the immune system. OVs are one promising alternative to conventional therapies in glioma tumor treatment. Several clinical trials have proven the feasibility of using some viruses to specifically infect tumors, eluding undesired toxic effects in the patient. Here, we revisited the literature to describe the main OVs proposed up to the present moment as therapeutic alternatives in order to destroy glioma cells in vitro and trigger tumor destruction in vivo. Oncolytic viruses were divided with respect to the genome in DNA and RNA viruses. Here, we highlight the results obtained in various clinical trials, which are exploring the use of these agents as an alternative where other approaches provide limited hope.
Topics: Animals; Brain Neoplasms; Clinical Trials as Topic; Glioma; Humans; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 33066689
DOI: 10.3390/ijms21207604 -
Biomedicine & Pharmacotherapy =... Feb 2021Oncolytic viruses have attracted attention as a promising strategy in cancer therapy owing to their ability to selectively infect and kill tumor cells, without affecting... (Review)
Review
Oncolytic viruses have attracted attention as a promising strategy in cancer therapy owing to their ability to selectively infect and kill tumor cells, without affecting healthy cells. They also exert their anti-tumor effects by releasing immunostimulatory molecules from dying cancer cells. Several regulatory mechanisms, such as autophagy, contribute to the anti-tumor properties of oncolytic viruses. Autophagy is a conserved catabolic process in responses to various stresses, such as nutrient deprivation, hypoxia, and infection that produces energy by lysosomal degradation of intracellular contents. Autophagy can support infectivity and replication of the oncolytic virus and enhance their anti-tumor effects via mediating oncolysis, autophagic cell death, and immunogenic cell death. On the other hand, autophagy can reduce the cytotoxicity of oncolytic viruses by providing survival nutrients for tumor cells. In his review, we summarize various types of oncolytic viruses in clinical trials, their mechanism of action, and autophagy machinery. Furthermore, we precisely discuss the interaction between oncolytic viruses and autophagy in cancer therapy and their combinational effects on tumor cells.
Topics: Adenoviridae; Animals; Autophagic Cell Death; Autophagy; Cell Line, Tumor; Clinical Trials as Topic; Humans; Immunogenic Cell Death; Measles virus; Mice; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Simplexvirus; Vesiculovirus; Virus Replication
PubMed: 33370632
DOI: 10.1016/j.biopha.2020.110932 -
Viruses Jul 2023Oncolytic viruses have positively impacted cancer immunotherapy over the past 20 years. Both natural and genetically modified viruses have shown promising results in... (Review)
Review
Oncolytic viruses have positively impacted cancer immunotherapy over the past 20 years. Both natural and genetically modified viruses have shown promising results in treating various cancers. Various regulatory authorities worldwide have approved four commercial oncolytic viruses, and more are being developed to overcome this limitation and obtain better anti-tumor responses in clinical trials at various stages. Faster advancements in translating research into the commercialization of cancer immunotherapy and a comprehensive understanding of the modification strategies will widen the current knowledge of future technologies related to the development of oncolytic viruses. In this review, we discuss the strategies of virus engineering and the progress of clinical trials to achieve virotherapeutics.
Topics: Oncolytic Viruses; Immunotherapy; Neoplasms
PubMed: 37631987
DOI: 10.3390/v15081645