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Human Vaccines & Immunotherapeutics Oct 2020Oncolytic viruses have been taking the front stage in biological therapy for cancer recently. The first and most potent virus to be used in oncolytic virotherapy is... (Review)
Review
Oncolytic viruses have been taking the front stage in biological therapy for cancer recently. The first and most potent virus to be used in oncolytic virotherapy is human adenovirus. Recently, ongoing extensive research has suggested that other viruses like herpes simplex virus (HSV) and measles virus can also be considered as potential candidates in cancer therapy. An HSV-based oncolytic virus, T-VEC, has completed phase Ш clinical trial and has been approved by the U.S. Food and Drug Administration (FDA) for use in biological cancer therapy. Moreover, the vaccine strain of the measles virus has shown impressive results in pre-clinical and clinical trials. Considering their therapeutic efficacy, safety, and reduced side effects, the use of such engineered viruses in biological cancer therapy has the potential to establish a milestone in cancer research. In this review, we summarize the recent clinical advances in the use of oncolytic viruses in biological therapy for cancer. Additionally, this review evaluates the potential viral candidates for their benefits and shortcomings and sheds light on the future prospects.
Topics: Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32078405
DOI: 10.1080/21645515.2020.1723363 -
Trends in Cancer Feb 2023Oncolytic viruses (OVs) provide novel and promising therapeutic options for patients with cancers resistant to traditional therapies. Natural or genetically modified OVs... (Review)
Review
Oncolytic viruses (OVs) provide novel and promising therapeutic options for patients with cancers resistant to traditional therapies. Natural or genetically modified OVs are multifaceted tumor killers. They directly lyse tumor cells while sparing normal cells, and indirectly potentiate antitumor immunity by releasing antigens and activating inflammatory responses in the tumor microenvironment. However, some limitations, such as limited penetration of OVs into tumors, short persistence, and the host antiviral immune response, are impeding the broad translation of oncolytic virotherapy into the clinic. If these challenges can be overcome, combination therapies, such as OVs plus immune checkpoint blockade (ICB), chimeric antigen receptor (CAR) T cells, or CAR natural killer (NK) cells, may provide powerful therapeutic platforms in the clinic.
Topics: Humans; Oncolytic Viruses; Immunotherapy; Oncolytic Virotherapy; Neoplasms; Killer Cells, Natural; Tumor Microenvironment
PubMed: 36402738
DOI: 10.1016/j.trecan.2022.10.003 -
Current Problems in Cancer Feb 2021Viruses as cancer therapies have attracted attention since the 19th century. Scientists observation that viruses can preferentially lyse cancer cells rather than healthy... (Review)
Review
Viruses as cancer therapies have attracted attention since the 19th century. Scientists observation that viruses can preferentially lyse cancer cells rather than healthy cells, created the field of oncolytic virology. Like other therapeutic strategies, oncolytic virotherapy has challenges, such as penetration into tumor bulk, anti-viral immune responses, off-target infection, adverse conditions in the tumor microenvironment, and the lack of specific predictive and therapeutic biomarkers. Whilst much progress has been made, as highlighted by the first Food and Drug Administration approval of an oncolytic virus talimogene laherparepvec (T-VEC) in 2015, addressing these issues remains a significant hurdle. Here we discuss different types of oncolytic viruses, their application in clinical trials, and finally challenges faced by the field of oncolytic virotherapy and strategies to overcome them.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 32828575
DOI: 10.1016/j.currproblcancer.2020.100639 -
Journal of Hematology & Oncology Jun 2020In this review, we discuss the use of oncolytic viruses in cancer immunotherapy treatments in general, with a particular focus on adenoviruses. These serve as a model to... (Review)
Review
In this review, we discuss the use of oncolytic viruses in cancer immunotherapy treatments in general, with a particular focus on adenoviruses. These serve as a model to elucidate how versatile viruses are, and how they can be used to complement other cancer therapies to gain optimal patient benefits. Historical reports from over a hundred years suggest treatment efficacy and safety with adenovirus and other oncolytic viruses. This is confirmed in more contemporary patient series and multiple clinical trials. Yet, while the first viruses have already been granted approval from several regulatory authorities, room for improvement remains.As good safety and tolerability have been seen, the oncolytic virus field has now moved on to increase efficacy in a wide array of approaches. Adding different immunomodulatory transgenes to the viruses is one strategy gaining momentum. Immunostimulatory molecules can thus be produced at the tumor with reduced systemic side effects. On the other hand, preclinical work suggests additive or synergistic effects with conventional treatments such as radiotherapy and chemotherapy. In addition, the newly introduced checkpoint inhibitors and other immunomodulatory drugs could make perfect companions to oncolytic viruses. Especially tumors that seem not to be recognized by the immune system can be made immunogenic by oncolytic viruses. Logically, the combination with checkpoint inhibitors is being evaluated in ongoing trials. Another promising avenue is modulating the tumor microenvironment with oncolytic viruses to allow T cell therapies to work in solid tumors.Oncolytic viruses could be the next remarkable wave in cancer immunotherapy.
Topics: Adenoviruses, Human; Antibodies, Viral; Antibody-Dependent Cell Cytotoxicity; Combined Modality Therapy; Cytotoxicity, Immunologic; Host-Pathogen Interactions; Humans; Immune Checkpoint Inhibitors; Immunologic Factors; Lymphocyte Activation; Lymphocyte Subsets; Lymphocytes, Tumor-Infiltrating; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Therapeutics; Transgenes; Tumor Microenvironment; Viral Tropism
PubMed: 32600470
DOI: 10.1186/s13045-020-00922-1 -
Viruses Feb 2023Glioblastoma is the most aggressive form of malignant brain tumor. Standard treatment protocols and traditional immunotherapy are poorly effective as they do not... (Review)
Review
Glioblastoma is the most aggressive form of malignant brain tumor. Standard treatment protocols and traditional immunotherapy are poorly effective as they do not significantly increase the long-term survival of glioblastoma patients. Oncolytic viruses (OVs) may be an effective alternative approach. Combining OVs with some modern treatment options may also provide significant benefits for glioblastoma patients. Here we review virotherapy for glioblastomas and describe several OVs and their combination with other therapies. The personalized use of OVs and their combination with other treatment options would become a significant area of research aiming to develop the most effective treatment regimens for glioblastomas.
Topics: Humans; Glioblastoma; Oncolytic Viruses; Immunotherapy; Brain Neoplasms
PubMed: 36851761
DOI: 10.3390/v15020547 -
Signal Transduction and Targeted Therapy Apr 2022Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells,... (Review)
Review
Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed. In addition to direct oncolysis, the essential and attractive aspect of oncolytic virotherapy is based on the intrinsic induction of both innate and adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered to express immune regulators that enhance or restore antitumor immunity. Recently, combinations of OVs with other immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptors (CARs), antigen-specific T-cell receptors (TCRs) and autologous tumor-infiltrating lymphocytes (TILs), have led to promising progress in cancer treatment. This review summarizes the intrinsic mechanisms of OVs, describes the optimization strategies for using armed OVs to enhance the effects of antitumor immunity and highlights rational combinations of OVs with other immunotherapies in recent preclinical and clinical studies.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Receptors, Chimeric Antigen
PubMed: 35387984
DOI: 10.1038/s41392-022-00951-x -
International Journal of Molecular... Sep 2021Oncolytic adenovirus therapy is gaining importance as a novel treatment option for the management of various cancers. Different concepts of modification within the... (Review)
Review
Oncolytic adenovirus therapy is gaining importance as a novel treatment option for the management of various cancers. Different concepts of modification within the adenovirus vector have been identified that define the mode of action against and the interaction with the tumour. Adenoviral vectors allow for genetic manipulations that restrict tumour specificity and also the expression of specific transgenes in order to support the anti-tumour effect. Additionally, replication of the virus and reinfection of neighbouring tumour cells amplify the therapeutic effect. Another important aspect in oncolytic adenovirus therapy is the virus induced cell death which is a process that activates the immune system against the tumour. This review describes which elements in adenovirus vectors have been identified for modification not only to utilize oncolytic adenovirus vectors into conditionally replicating adenoviruses (CRAds) that allow replication specifically in tumour cells but also to confer specific characteristics to these viruses. These advances in development resulted in clinical trials that are summarized based on the conceptual design.
Topics: Adenoviridae; Animals; Clinical Trials as Topic; Genetic Vectors; Humans; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Outcome Assessment, Health Care; Virus Replication
PubMed: 34638863
DOI: 10.3390/ijms221910522 -
Journal of Medical Virology Apr 2023Oncolytic viruses (OVs) can selectively kill tumor cells without affecting normal cells, as well as activate the innate and adaptive immune systems in patients. Thus,... (Review)
Review
Oncolytic viruses (OVs) can selectively kill tumor cells without affecting normal cells, as well as activate the innate and adaptive immune systems in patients. Thus, they have been considered as a promising measure for safe and effective cancer treatment. Recently, a few genetically engineered OVs have been developed to further improve the effect of tumor elimination by expressing specific immune regulatory factors and thus enhance the body's antitumor immunity. In addition, the combined therapies of OVs and other immunotherapies have been applied in clinical. Although there are many studies on this hot topic, a comprehensive review is missing on illustrating the mechanisms of tumor clearance by OVs and how to modify engineered OVs to further enhance their antitumor effects. In this study, we provided a review on the mechanisms of immune regulatory factors in OVs. In addition, we reviewed the combined therapies of OVs with other therapies including radiotherapy and CAR-T or TCR-T cell therapy. The review is useful in further generalize the usage of OV in cancer treatment.
Topics: Humans; Oncolytic Viruses; Oncolytic Virotherapy; Neoplasms; Immunotherapy; Immunologic Factors
PubMed: 37185868
DOI: 10.1002/jmv.28729 -
Nature Communications Jul 2023The codependency of cholesterol metabolism sustains the malignant progression of glioblastoma (GBM) and effective therapeutics remain scarce. In orthotopic GBM models in...
The codependency of cholesterol metabolism sustains the malignant progression of glioblastoma (GBM) and effective therapeutics remain scarce. In orthotopic GBM models in male mice, we identify that codependent cholesterol metabolism in tumors induces phagocytic dysfunction in monocyte-derived tumor-associated macrophages (TAMs), resulting in disease progression. Manipulating cholesterol efflux with apolipoprotein A1 (ApoA1), a cholesterol reverse transporter, restores TAM phagocytosis and reactivates TAM-T cell antitumor immunity. Cholesterol metabolomics analysis of in vivo-sorted TAMs further reveals that ApoA1 mediates lipid-related metabolic remodeling and lowers 7-ketocholesterol levels, which directly inhibits tumor necrosis factor signaling in TAMs through mitochondrial translation inhibition. An ApoA1-armed oncolytic adenovirus is also developed, which restores antitumor immunity and elicits long-term tumor-specific immune surveillance. Our findings provide insight into the mechanisms by which cholesterol metabolism impairs antitumor immunity in GBM and offer an immunometabolic approach to target cholesterol disturbances in GBM.
Topics: Male; Mice; Animals; Glioblastoma; Oncolytic Viruses; Tumor-Associated Macrophages; Phagocytosis; Cholesterol; Tumor Microenvironment
PubMed: 37474548
DOI: 10.1038/s41467-023-39683-z -
Signal Transduction and Targeted Therapy Apr 2023Oncolytic viruses (OVs) have attracted growing awareness in the twenty-first century, as they are generally considered to have direct oncolysis and cancer immune... (Review)
Review
Oncolytic viruses (OVs) have attracted growing awareness in the twenty-first century, as they are generally considered to have direct oncolysis and cancer immune effects. With the progress in genetic engineering technology, OVs have been adopted as versatile platforms for developing novel antitumor strategies, used alone or in combination with other therapies. Recent studies have yielded eye-catching results that delineate the promising clinical outcomes that OVs would bring about in the future. In this review, we summarized the basic principles of OVs in terms of their classifications, as well as the recent advances in OV-modification strategies based on their characteristics, biofunctions, and cancer hallmarks. Candidate OVs are expected to be designed as "qualified soldiers" first by improving target fidelity and safety, and then equipped with "cold weapons" for a proper cytocidal effect, "hot weapons" capable of activating cancer immunotherapy, or "auxiliary weapons" by harnessing tactics such as anti-angiogenesis, reversed metabolic reprogramming and decomposing extracellular matrix around tumors. Combinations with other cancer therapeutic agents have also been elaborated to show encouraging antitumor effects. Robust results from clinical trials using OV as a treatment congruously suggested its significance in future application directions and challenges in developing OVs as novel weapons for tactical decisions in cancer treatment.
Topics: Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 37041165
DOI: 10.1038/s41392-023-01407-6