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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 -
Cancer Medicine May 2023Despite great medical advances, oncological research is still looking for novel therapeutic approaches due to the limitation of conventional therapeutic agents.... (Review)
Review
Despite great medical advances, oncological research is still looking for novel therapeutic approaches due to the limitation of conventional therapeutic agents. Virotherapy is one of these new emerging therapeutic approaches that attract attention with their widespread applications. Virotherapy use lives oncolytic viruses or genetically engineered viruses that selectively infect the tumor cells, replicate, and disrupt the cancerous cells that also induce their anticancer activity by stimulating the host antitumor immune response. Moreover, viruses are widely used as target delivery vectors for specifically delivering different genes, therapeutic agents, and immune-stimulating agents. In addition to having antitumor activity by themselves in combination with conventional therapeutic agents like immune therapy and chemotherapy, Virotherapy agents also elicit promising outcomes. Therefore, in addition to their promising result in monotherapy use, virotherapy agents can also be used in combination with conventional cancer therapy, epigenetic modulators, and even microRNAs without any cross-resistance, which allows the patient not to be deprived of her routine medicine. Still, this combination therapy reduces the adverse effect of the conventional therapies. All together suggest that virotherapy agents as novel potential agents in the field of cancer therapy.
Topics: Humans; Oncolytic Virotherapy; Neoplasms; Oncolytic Viruses; Viruses; Combined Modality Therapy
PubMed: 36880311
DOI: 10.1002/cam4.5694 -
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 -
BMC Immunology Dec 2018Oncolytic viruses have been proposed to be employed as a potential treatment of cancer. Well targeted, they will serve the purpose of cracking tumor cells without... (Review)
Review
BACKGROUND
Oncolytic viruses have been proposed to be employed as a potential treatment of cancer. Well targeted, they will serve the purpose of cracking tumor cells without causing damage to normal cells. In this category of oncolytic viral drugs human pathogens herpes simplex virus (HSV) is especially suitable for the cause. Although most viral infection causes antiviral reaction in the host, HSV has multiple mechanisms to evade those responses. Powerful anti-tumor effect can thus be achieved via genetic manipulation of the HSV genes involved in this evading mechanism, namely deletions or mutations that adapt its function towards a tumor microenvironment. Currently, oncolytic HSV (oHSV) is widely use in clinical; moreover, there's hope that its curative effect will be further enhanced through the combination of oHSV with both traditional and emerging therapeutics.
RESULTS
In this review, we provide a summary of the HSV host antiviral response evasion mechanism, HSV expresses immune evasion genes such as ICP34.5, ICP0, Us3, which are involved in inducing and activating host responses, so that the virus can evade the immune system and establish effective long-term latent infection; we outlined details of the oHSV strains generated by removing genes critical to viral replication such as ICP34.5, ICP0, and inserting therapeutic genes such as LacZ, granulocyte macrophage colony-stimulating factor (GM-CSF); security and limitation of some oHSV such G207, 1716, OncoVEX, NV1020, HF10, G47 in clinical application; and the achievements of oHSV combined with immunotherapy and chemotherapy.
CONCLUSION
We reviewed the immunotherapy mechanism of the oHSV and provided a series of cases. We also pointed out that an in-depth study of the application of oHSV in cancer treatment will potentially benefits cancer patients more.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Simplexvirus
PubMed: 30563466
DOI: 10.1186/s12865-018-0281-9 -
Journal For Immunotherapy of Cancer Feb 2021The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving... (Review)
Review
The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic 'cold' tumors into inflamed immunogenic 'hot' tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.
Topics: Humans; Immunotherapy; Mesenchymal Stem Cells; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 33558278
DOI: 10.1136/jitc-2020-001684 -
Human Vaccines & Immunotherapeutics May 2017
Topics: Drug Evaluation, Preclinical; Humans; Neoplasm Metastasis; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 28384050
DOI: 10.1080/21645515.2017.1298962 -
Viruses Nov 2015Adenoviruses (Ad) are commonly used both experimentally and clinically, including oncolytic virotherapy applications. In the clinical area, efficacy is frequently... (Review)
Review
Adenoviruses (Ad) are commonly used both experimentally and clinically, including oncolytic virotherapy applications. In the clinical area, efficacy is frequently hampered by the high rates of neutralizing immunity, estimated as high as 90% in some populations that promote vector clearance and limit bioavailability for tumor targeting following systemic delivery. Active tumor targeting is also hampered by the ubiquitous nature of the Ad5 receptor, hCAR, as well as the lack of highly tumor-selective targeting ligands and suitable targeting strategies. Furthermore, significant off-target interactions between the viral vector and cellular and proteinaceous components of the bloodstream have been documented that promote uptake into non-target cells and determine dose-limiting toxicities. Novel strategies are therefore needed to overcome the obstacles that prevent efficacious Ad deployment for wider clinical applications. The use of less seroprevalent Ad serotypes, non-human serotypes, capsid pseudotyping, chemical shielding and genetic masking by heterologous peptide incorporation are all potential strategies to achieve efficient vector escape from humoral immune recognition. Conversely, selective vector arming with immunostimulatory agents can be utilized to enhance their oncolytic potential by activation of cancer-specific immune responses against the malignant tissues. This review presents recent advantages and pitfalls occurring in the field of adenoviral oncolytic therapies.
Topics: Adenoviridae; Animals; Humans; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 26610547
DOI: 10.3390/v7112923 -
Cytokine & Growth Factor Reviews Jun 2018Oncolytic viruses (OVs), viruses that specifically result in killing tumor cells, represent a promising class of cancer therapy. Recently, the focus in the OV therapy... (Review)
Review
Oncolytic viruses (OVs), viruses that specifically result in killing tumor cells, represent a promising class of cancer therapy. Recently, the focus in the OV therapy field has shifted from their direct oncolytic effect to their immune stimulatory effect. OV therapy can function as a "kick start" for the antitumor immune response by releasing tumor associated antigens and release of inflammatory signals. Combining OVs with immune modulators could enhance the efficacy of both immune and OV therapies. Additionally, genetic engineering of OVs allows local expression of immune therapeutics, thereby reducing related toxicities. Different options to modify the tumor microenvironment in combination with OV therapy have been explored. The possibilities and obstacles of these combinations will be discussed in this review.
Topics: Animals; Antineoplastic Agents; Humans; Immunologic Factors; Neoplasms; Oncolytic Viruses; Tumor Microenvironment
PubMed: 29576283
DOI: 10.1016/j.cytogfr.2018.03.006 -
Viruses Jul 2021Oncolytic herpes simplex virus (oHSV) is a therapeutic modality that has seen substantial success for the treatment of cancer, though much remains to be improved.... (Review)
Review
Oncolytic herpes simplex virus (oHSV) is a therapeutic modality that has seen substantial success for the treatment of cancer, though much remains to be improved. Commonly attenuated through the deletion or alteration of the γ34.5 neurovirulence gene, the basis for the success of oHSV relies in part on the malignant silencing of cellular pathways critical for limiting these viruses in healthy host tissue. However, only recently have the molecular mechanisms underlying the success of these treatments begun to emerge. Further clarification of these mechanisms can strengthen rational design approaches to develop the next generation of oHSV. Herein, we review our current understanding of the molecular basis for tumor susceptibility to γ34.5-attenuated oHSV, with particular focus on the malignant suppression of nucleic acid sensing, along with strategies meant to improve the clinical efficacy of these therapeutic viruses.
Topics: Animals; Cytokines; Herpesvirus 1, Human; Host Microbial Interactions; Humans; Mice; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 34372614
DOI: 10.3390/v13071408 -
International Journal of Molecular... Nov 2020Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k... (Review)
Review
Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has been renewed interest in IO. In the past decade, ICIs have changed the treatment paradigm for many cancers by enabling better therapeutic control, resuming immune surveillance, suppressing tumor immunosuppression, and restoring antitumor immune function. However, ICI therapies are effective only in a small subset of patients and show limited therapeutic potential due to their inability to demonstrate efficacy in 'cold' or unresponsive tumor microenvironments (TMEs). Relatedly, oncolytic viruses (OVs) have been shown to induce antitumor immune responses, augment the efficacy of existing cancer treatments, and reform unresponsive TME to turn 'cold' tumors 'hot,' increasing their susceptibility to checkpoint blockade immunotherapies. For this reason, OVs serve as ideal complements to ICIs, and multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy. This review will discuss the merits and limitations of OVs and ICIs as monotherapy then progress onto the preclinical rationale and the results of clinical trials of key combination therapies.
Topics: Clinical Trials as Topic; Humans; Immune Checkpoint Inhibitors; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Tumor Microenvironment
PubMed: 33207653
DOI: 10.3390/ijms21228627