-
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 -
Nature Reviews. Drug Discovery Sep 2015Oncolytic viruses represent a new class of therapeutic agents that promote anti-tumour responses through a dual mechanism of action that is dependent on selective tumour... (Review)
Review
Oncolytic viruses represent a new class of therapeutic agents that promote anti-tumour responses through a dual mechanism of action that is dependent on selective tumour cell killing and the induction of systemic anti-tumour immunity. The molecular and cellular mechanisms of action are not fully elucidated but are likely to depend on viral replication within transformed cells, induction of primary cell death, interaction with tumour cell antiviral elements and initiation of innate and adaptive anti-tumour immunity. A variety of native and genetically modified viruses have been developed as oncolytic agents, and the approval of the first oncolytic virus by the US Food and Drug Administration (FDA) is anticipated in the near future. This Review provides a comprehensive overview of the basic biology supporting oncolytic viruses as cancer therapeutic agents, describes oncolytic viruses in advanced clinical trials and discusses the unique challenges in the development of oncolytic viruses as a new class of drugs for the treatment of cancer.
Topics: Animals; Humans; Immunologic Factors; Immunotherapy; Neoplasms; Oncolytic Viruses
PubMed: 26323545
DOI: 10.1038/nrd4663 -
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 -
Cancer Science Oct 2016Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic... (Review)
Review
Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe. The phase III trial proved that local intralesional injections with T-Vec in advanced malignant melanoma patients can not only suppress the growth of injected tumors but also act systemically and prolong overall survival. Other oncolytic viruses that are closing in on drug approval in North America and Europe include vaccinia virus JX-594 (pexastimogene devacirepvec) for hepatocellular carcinoma, GM-CSF-expressing adenovirus CG0070 for bladder cancer, and Reolysin (pelareorep), a wild-type variant of reovirus, for head and neck cancer. In Japan, a phase II clinical trial of G47∆, a third-generation oncolytic HSV-1, is ongoing in glioblastoma patients. G47∆ was recently designated as a "Sakigake" breakthrough therapy drug in Japan. This new system by the Japanese government should provide G47∆ with priority reviews and a fast-track drug approval by the regulatory authorities. Whereas numerous oncolytic viruses have been subjected to clinical trials, the common feature that is expected to play a major role in prolonging the survival of cancer patients is an induction of specific antitumor immunity in the course of tumor-specific viral replication. It appears that it will not be long before oncolytic virus therapy becomes a standard therapeutic option for all cancer patients.
Topics: Animals; Clinical Trials as Topic; Genetic Engineering; Genetic Therapy; Genetic Vectors; Humans; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Treatment Outcome
PubMed: 27486853
DOI: 10.1111/cas.13027 -
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 -
Journal For Immunotherapy of Cancer Dec 2018Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with... (Review)
Review
BACKGROUND
Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques.
MAIN BODY
The ability to deliver therapy tailored to specific cellular targets at the precise locus in which it would have its greatest impact is a profound development in anti-cancer treatment. Although immune checkpoint inhibitors have an improved tolerability profile relative to cytotoxic chemotherapy and whole beam radiation, severe immune-related adverse events have emerged as a potential limitation. These include pneumonitis, pancreatitis, and colitis, which are relatively infrequent but can limit therapeutic options for some patients. Intratumor injection of oncolytic viruses, in contrast, has a markedly lower rate of serious adverse effects and perhaps greater specificity to target tumor cells. Early stage clinical trials using oncolytic viruses show induction of effector anti-tumor immune responses and suggest that such therapies could also morph and redefine both the local target cells' niche as well as impart distant effects on remote cells with a similar molecular profile.
CONCLUSION
It is imperative for the modern immuno-oncologist to understand the biological processes underlying the immune dysregulation in cancer as well as the effects, uses, and limitations of oncolytic viruses. It will be with this foundational understanding that the future of oncolytic viral therapies and their delivery can be refined to forge future horizons in the direct modulation of the tumor bed.
Topics: Animals; Cancer Vaccines; Combined Modality Therapy; Gene Transfer Techniques; Genetic Vectors; Humans; Immunologic Surveillance; Immunomodulation; Immunotherapy; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Treatment Outcome; Tumor Escape
PubMed: 30514385
DOI: 10.1186/s40425-018-0458-z -
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 For Immunotherapy of Cancer Oct 2020Oncolytic viruses (OVs) are a new class of cancer therapeutics. This review was undertaken to provide insight into the current landscape of OV clinical trials. A PubMed... (Review)
Review
Oncolytic viruses (OVs) are a new class of cancer therapeutics. This review was undertaken to provide insight into the current landscape of OV clinical trials. A PubMed search identified 119 papers from 2000 to 2020 with 97 studies reporting data on 3233 patients. The viruses used, presence of genetic modifications and/or transgene expression, cancer types targeted, inclusion of combination strategies and safety profile were reported. In addition, information on viral bioshedding across the studies, including which tissues or body fluids were evaluated and how virus was detected (eg, PCR, plaque assay or both), is also reported. Finally, the number of studies evaluating antiviral and antitumor humoral and cellular immune responses were noted. We found that adenovirus (n=30) is the most common OV in clinical trials with approximately two-thirds (n=63) using modified or recombinant viral backbones and granulocyte-macrophage colony-stimulating factor (n=24) was the most common transgene. The most common tumors targeted were melanoma (n=1000) and gastrointestinal (GI; n=577) cancers with most using monotherapy OVs given by intratumoral (n=1482) or intravenous (n=1347) delivery. The most common combination included chemotherapy (n=36). Overall, OV treatment-related adverse events were low-grade constitutional and local injection site reactions. Viral shedding was frequently measured although many studies restricted this to blood and tumor tissue and used PCR only. While most studies did report antiviral antibody titers (n=63), only a minority of studies reported viral-specific T cell responses (n=10). Tumor immunity was reported in 48 studies and largely relied on general measures of immune activation (eg, tumor biopsy immunohistochemistry (n=25) and serum cytokine measurement (n=19)) with few evaluating tumor-specific immune responses (n=7). Objective responses were reported in 292 (9%) patients and disease control was achieved in 681 (21.1%) patients, although standard reporting criteria were only used in 53% of the trials. Completed clinical trials not reported in the peer-reviewed literature were not included in this review potentially underestimating the impact of OV treatment. These data provide insight into the current profile of OV clinical trials reporting and identifies potential gaps where further studies are needed to better define the role of OVs, alone and in combination, for patients with cancer.
Topics: Biomedical Research; History, 21st Century; Humans; Immunotherapy; Oncolytic Virotherapy; Oncolytic Viruses
PubMed: 33046622
DOI: 10.1136/jitc-2020-001486