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International Journal of Molecular... Mar 2021Many immuno-therapeutic strategies are currently being developed to fight cancer. In this scenario, oncolytic adenoviruses (Onc.Ads) have an interesting role for their... (Review)
Review
Many immuno-therapeutic strategies are currently being developed to fight cancer. In this scenario, oncolytic adenoviruses (Onc.Ads) have an interesting role for their peculiar tumor selectivity, safety, and transgene-delivery capability. The major strength of the Onc.Ads is the extraordinary immunogenicity that leads to a strong T-cell response, which, together with the possibility of the delivery of a therapeutic transgene, could be more effective than current strategies. In this review, we travel in the adenovirus (Ads) and Onc.Ads world, focusing on a variety of strategies that can enhance Onc.Ads antitumoral efficacy, passing through tumor microenvironment modulation. Onc.Ads-based therapeutic strategies constitute additional weapons in the fight against cancer and appear to potentiate conventional and immune checkpoint inhibitors (ICIs)-based therapies leading to a promising scenario.
Topics: Adenoviridae; Animals; Genetic Therapy; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; T-Lymphocytes; Tumor Microenvironment
PubMed: 33802281
DOI: 10.3390/ijms22052517 -
Cancer Biology & Medicine Aug 2023Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects systemic administration. Tumor cells often... (Review)
Review
Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects systemic administration. Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication; however, recent studies have established that viruses altered genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments. Specifically, oncolytic vaccinia virus (OVV) has gained popularity owing to its safety, potential for systemic delivery, and large gene insertion capacity. This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity and , and provides an overview of ongoing clinical trials and combination therapies. In addition, we discuss the potential benefits and drawbacks of OVV as a cancer therapy, and explore different perspectives in this field.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment; Vaccinia virus; Clinical Trials as Topic
PubMed: 37615308
DOI: 10.20892/j.issn.2095-3941.2023.0202 -
Journal For Immunotherapy of Cancer Aug 2023Oncolytic viruses (OVs) provide the promise of tumor-selective cytotoxicity coupled with amplification of the therapeutic agent (the virus) within the tumor improving... (Review)
Review
Oncolytic viruses (OVs) provide the promise of tumor-selective cytotoxicity coupled with amplification of the therapeutic agent (the virus) within the tumor improving its therapeutic index. Despite this promise, however, single agent-treatments have not been as successful as combination therapies, particularly combining with checkpoint inhibitor antibodies. The antibodies may be delivered by two approaches, either encoded within the OV genome to restrict antibody production to sites of active virus infection or alternatively given alongside OVs as separate treatments. Both approaches have shown promising therapeutic outcomes, and this leads to an interesting question of whether one approach is potentially better than the other. In this review, we provide a brief summary of the combination OV-antibody therapies that target tumor cells, tumor microenvironment and immune cells to help define key parameters influencing which approach is superior, thereby improving insight into the rational design of OV treatment strategies.
Topics: Humans; Oncolytic Viruses; Oncolytic Virotherapy; Neoplasms; Immunotherapy; Antibodies; Tumor Microenvironment
PubMed: 37541690
DOI: 10.1136/jitc-2022-006518 -
American Journal of Clinical Dermatology Feb 2017Many mammalian viruses have properties that can be commandeered for the treatment of cancer. These characteristics include preferential infection and replication in... (Review)
Review
Many mammalian viruses have properties that can be commandeered for the treatment of cancer. These characteristics include preferential infection and replication in tumor cells, the initiation of tumor cell lysis, and the induction of innate and adaptive anti-tumor immunity. Furthermore, viruses can be genetically engineered to reduce pathogenicity and increase immunogenicity resulting in minimally toxic therapeutic agents. Talimogene laherparepvec (T-VEC; Imlygic™), is a genetically modified herpes simplex virus, type 1, and is the first oncolytic virus therapy to be approved for the treatment of advanced melanoma by the US FDA. T-VEC is attenuated by the deletion of the herpes neurovirulence viral genes and enhanced for immunogenicity by the deletion of the viral ICP47 gene. Immunogenicity is further supported by expression of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, which helps promote the priming of T cell responses. T-VEC demonstrated significant improvement in durable response rate, objective response rate, and progression-free survival in a randomized phase III clinical trial for patients with advanced melanoma. This review will discuss the optimal selection of patients for such treatment and describe how therapy is optimally delivered. We will also discuss future directions for oncolytic virus immunotherapy, which will likely include combination T-VEC clinical trials, expansion of T-VEC to other types of non-melanoma skin cancers, and renewed efforts at oncolytic virus drug development with other viruses.
Topics: Animals; Humans; Immunotherapy; Melanoma; Oncolytic Virotherapy; Oncolytic Viruses; Patient Selection; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 27988837
DOI: 10.1007/s40257-016-0238-9 -
Molecular Therapy : the Journal of the... Jun 2022Cancer is a disease caused by loss of regulatory processes that control the cell cycle, resulting in increased proliferation. The loss of control can deregulate both... (Review)
Review
Cancer is a disease caused by loss of regulatory processes that control the cell cycle, resulting in increased proliferation. The loss of control can deregulate both tumor suppressors and oncogenes. Apart from cell intrinsic gene mutations and environmental factors, infection by cancer-causing viruses also induces changes that lead to malignant transformation. This can be caused by both expression of oncogenic viral proteins and also by changes in cellular genes and proteins that affect the epigenome. Thus, these epigenetic modifiers are good therapeutic targets, and several epigenetic inhibitors are approved for the treatment of different cancers. In addition to small molecule drugs, biological therapies, such as antibodies and viral therapies, are also increasingly being used to treat cancer. An HSV-1-derived oncolytic virus is currently approved by the US FDA and the European Medicines Agency. Similarly, an adenovirus-based therapeutic is approved for use in China for some cancer types. Because viruses can affect cellular epigenetics, the interaction of epigenome-targeting drugs with oncogenic and oncolytic viruses is a highly significant area of investigation. Here, we will review the current knowledge about the impact of using epigenetic drugs in tumors positive for oncogenic viruses or as therapeutic combinations with oncolytic viruses.
Topics: Histones; Humans; Neoplasms; Oncogenic Viruses; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 35143960
DOI: 10.1016/j.ymthe.2022.02.006 -
Nature Communications Oct 2023IDH1 mutations frequently occur early in human glioma. While IDH1 mutation has been shown to promote gliomagenesis via DNA and histone methylation, little is known...
IDH1 mutations frequently occur early in human glioma. While IDH1 mutation has been shown to promote gliomagenesis via DNA and histone methylation, little is known regarding its regulation in antiviral immunity. Here, we discover that IDH1 mutation inhibits virus-induced interferon (IFN) antiviral responses in glioma cells. Mechanistically, D2HG produced by mutant IDH1 enhances the binding of DNMT1 to IRF3/7 promoters such that IRF3/7 are downregulated, leading to impaired type I IFN response in glioma cells, which enhances the susceptibility of gliomas to viral infection. Furthermore, we identify DNMT1 as a potential biomarker predicting which IDH1mut gliomas are most likely to respond to oncolytic virus. Finally, both D2HG and ectopic mutant IDH1 can potentiate the replication and oncolytic efficacy of VSVΔ51 in female mouse models. These findings reveal a pivotal role for IDH1 mutation in regulating antiviral response and demonstrate that IDH1 mutation confers sensitivity to oncolytic virotherapy.
Topics: Animals; Female; Humans; Mice; Brain Neoplasms; Glioma; Isocitrate Dehydrogenase; Methylation; Mutation; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 37880243
DOI: 10.1038/s41467-023-42545-3 -
Cell Communication and Signaling : CCS Sep 2023Mesenchymal stem cells (MSCs) have attracted considerable interest as a promising approach for cancer treatment due to their ability to undergo tumor-trophic migration.... (Review)
Review
Mesenchymal stem cells (MSCs) have attracted considerable interest as a promising approach for cancer treatment due to their ability to undergo tumor-trophic migration. MSCs possess the unique ability to selectively migrate to tumors, making them an excellent candidate for targeted delivery of oncolytic viruses (OVs) to treat isolated tumors and metastatic malignancies. OVs have attracted attention as a potential treatment for cancer due to their ability to selectively infect and destroy tumor cells while sparing normal cells. In addition, OVs can induce immunogenic cell death and contain curative transgenes in their genome, making them an attractive candidate for cancer treatment in combination with immunotherapies. In combination with MSCs, OVs can modulate the tumor microenvironment and trigger anti-tumor immune responses, making MSC-releasing OVs a promising approach for cancer treatment. This study reviews researches on the use of MSC-released OVs as a novel method for treating cancer. Video Abstract.
Topics: Oncolytic Viruses; Immunotherapy; Immunogenic Cell Death; Mesenchymal Stem Cells; Tumor Microenvironment; Neoplasms
PubMed: 37667271
DOI: 10.1186/s12964-023-01232-y -
Viruses Jul 2021Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic... (Review)
Review
Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood-brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood-brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Glioblastoma; Glioma; Humans; Immunotherapy; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 34372501
DOI: 10.3390/v13071294 -
Expert Opinion on Biological Therapy Mar 2017Oncolytic viruses represent a novel treatment modality that is unencumbered by the standard resistance mechanisms limiting the therapeutic efficacy of conventional... (Review)
Review
Oncolytic viruses represent a novel treatment modality that is unencumbered by the standard resistance mechanisms limiting the therapeutic efficacy of conventional antineoplastic agents. Attenuated engineered measles virus strains derived from the Edmonston vaccine lineage have undergone extensive preclinical evaluation with significant antitumor activity observed in a broad range of preclinical tumoral models. These have laid the foundation for several clinical trials in both solid and hematologic malignancies, which have demonstrated safety, biologic activity and the ability to elicit antitumor immune responses. Areas covered: This review examines the published preclinical data which supported the clinical translation of this therapeutic platform, reviews the available clinical trial data and expands on ongoing phase II testing. It also looks at approaches to optimize clinical applicability and offers future perspectives. Expert opinion: Reverse genetic engineering has allowed the generation of oncolytic MV strains retargeted to increase viral tumor specificity, or armed with therapeutic and immunomodulatory genes in order to enhance anti-tumor efficacy. Continuous efforts focusing on exploring methods to overcome resistance pathways and determining optimal combinatorial strategies will facilitate further development of this encouraging antitumor strategy.
Topics: Animals; Genetic Engineering; Humans; Measles virus; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 28129716
DOI: 10.1080/14712598.2017.1288713 -
Current Oncology (Toronto, Ont.) Dec 2020The use of viruses for tumour treatment has been imagined more than one hundred years ago, when it was reported that viral diseases were occasionally leading to a... (Review)
Review
The use of viruses for tumour treatment has been imagined more than one hundred years ago, when it was reported that viral diseases were occasionally leading to a decrease in neoplastic lesions. Oncolytic viruses (OVs) seem to have a specific tropism for tumour cells. Previously, it was hypothesised that OVs' antineoplastic actions were mainly due to their ability to contaminate, proliferate and destroy tumour cells and the immediate destructive effect on cells was believed to be the single mechanism of action of OVs' action. Instead, it has been established that oncolytic viruses operate via a multiplicity of systems, including mutation of tumour milieu and a composite change of the activity of immune effectors. Oncolytic viruses redesign the tumour environment towards an antitumour milieu. The aim of our work is to evaluate the findings present in the literature about the use of OVs in the cure of haematological neoplastic pathologies such as multiple myeloma, acute and chronic myeloid leukaemia, and lymphoproliferative diseases. Further experimentations are essential to recognize the most efficient virus or treatment combinations for specific haematological diseases, and the combinations able to induce the strongest immune response.
Topics: Hematologic Neoplasms; Humans; Immunotherapy; Multiple Myeloma; Oncolytic Virotherapy; Oncolytic Viruses; Pharmaceutical Preparations
PubMed: 33704184
DOI: 10.3390/curroncol28010019