The Experts below are selected from a list of 26094 Experts worldwide ranked by ideXlab platform
Howard L. Kaufman - One of the best experts on this subject based on the ideXlab platform.
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generation and validation of recombinant herpes simplex type 1 viruses hsv 1 using crispr cas9 genetic disruption
Methods in Enzymology, 2020Co-Authors: Praveen K. Bommareddy, Cole Peters, Howard L. KaufmanAbstract:Abstract Herpes simplex virus type 1 (HSV-1) is a large DNA virus that has been popular for Oncolytic virus development in pre-clinical research and clinical trials. An Oncolytic HSV-1 encoding granulocyte-macrophage colony stimulating factor (GM-CSF), designated talimogene laherparepvec (T-VEC) was approved for the treatment of patients with advanced melanoma in 2015. There are numerous advantages of HSV-1 for Oncolytic development, including the ease of recombinant engineering, presence of non-essential genes allowing attenuation of pathogenicity and space for foreign transgene expression. In addition, most recombinants retain sensitivity to acyclovir providing an additional safety feature. In this chapter, we will focus on the key methods for the development of Oncolytic HSV-1 vectors and some of the commonly utilized laboratory protocols used to characterize and assess the structure and Oncolytic activity of recombinant HSV-1 viruses.
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Integrating Oncolytic viruses in combination cancer immunotherapy
Nature reviews. Immunology, 2018Co-Authors: Praveen K. Bommareddy, Megha Shettigar, Howard L. KaufmanAbstract:Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancer-immunity cycle. Oncolytic viruses directly lyse tumour cells, leading to the release of soluble antigens, danger signals and type I interferons, which drive antitumour immunity. In addition, some Oncolytic viruses can be engineered to express therapeutic genes or can functionally alter tumour-associated endothelial cells, further enhancing T cell recruitment into immune-excluded or immune-deserted tumour microenvironments. Oncolytic viruses can also utilize established tumours as an in situ source of neoantigen vaccination through cross-presentation, resulting in regression of distant, uninfected tumours. These features make Oncolytic viruses attractive agents for combination strategies to optimize cancer immunotherapy.
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Oncolytic viruses: a new class of immunotherapy drugs
Nature reviews. Drug discovery, 2015Co-Authors: Howard L. Kaufman, Frederick J. Kohlhapp, Andrew ZlozaAbstract:Oncolytic viruses can kill tumour cells through a dual mechanism of action; the direct lysis of cells, and the induction of an immune response. The first Oncolytic virus has been approved in China, and another has been recommended for approval in the United States. This Review discusses the biology of Oncolytic viruses as well as key Oncolytic viruses in clinical development, and investigates the challenges associated with developing Oncolytic viruses as a new therapeutic modality for cancer.
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Oncolytic viruses: a new class of immunotherapy drugs
Nature Reviews Drug Discovery, 2015Co-Authors: Howard L. Kaufman, Frederick J. Kohlhapp, Andrew ZlozaAbstract:Oncolytic viruses can kill tumour cells through a dual mechanism of action; the direct lysis of cells, and the induction of an immune response. The first Oncolytic virus has been approved in China, and another has been recommended for approval in the United States. This Review discusses the biology of Oncolytic viruses as well as key Oncolytic viruses in clinical development, and investigates the challenges associated with developing Oncolytic viruses as a new therapeutic modality for cancer. 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. Oncolytic viruses mediate anti-tumour responses through a dual mechanism involving viral oncolysis of cancer cells and induction of host 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, release of danger signals and initiation of innate and adaptive anti-tumour immunity. A variety of native and genetically modified viruses have been utilized as Oncolytic vectors in preclinical studies, which have demonstrated therapeutic activity against several types of cancer. Oncolytic viruses can be genetically modified to decrease pathogenicity, increase lytic potential and enhance immunogenicity, improving the risk–benefit ratio for clinical development. The approval of a modified adenovirus, H101, in China and the pending approval of a modified herpes simplex virus type 1 (HSV-1) encoding granulocyte–macrophage colony stimulating factor (GM-CSF), termed talimogene laherparepvec (T-VEC), by the US Food and Drug Administration (FDA) in the United States is likely to promote further drug development within this new class of cancer therapeutics. Oncolytic viruses face unique challenges in drug development, including the need for optimal clinical trial designs and response assessment that capture therapeutic responses, different regulatory and commercialization pathways, the need for live culture scale-up procedures, and novel biosafety concerns related to viral persistence in patients and transmission to household contacts and health-care providers.
Tomoki Todo - One of the best experts on this subject based on the ideXlab platform.
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Oncolytic virotherapy with socs3 enhances viral replicative potency and oncolysis for gastric cancer
Oncotarget, 2021Co-Authors: Shuichi Matsumura, Hiroshi Fukuhara, Tomoki Todo, Yasushi Ino, Mikihito Nakamori, Toshiaki Tsuji, Tomoya Kato, Masaki Nakamura, Toshiyasu Ojima, Hiroki YamaueAbstract:Oncolytic virotherapy is an encouraging treatment using herpes simplex virus (HSV) for gastric cancer patients. To treat gastric cancer, we generated and evaluated the efficacy of an attractive type of Oncolytic HSV expressing the suppressor of cytokine signaling 3 (SOCS3). We constructed a third-generation type of Oncolytic HSV (T-SOCS3) arming with SOCS3 by a bacterial artificial chromosome (BAC) system. We examined the viral replicative intensification and oncolysis of T-SOCS3 for human gastric cancer cell lines ex vivo. T-SOCS3 enhanced its replication and potentiated its cell-killing effect for MKN1 human gastric cancer cell lines, which are resistant to a non-armed third-generation type of Oncolytic HSV (T-01) ex vivo. T-SOCS3 also induced the destruction within human gastric cancer specimens. Armed Oncolytic HSVs expressing SOCS3 may be an efficacious therapeutic agent for gastric cancer treatment.
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Oncolytic virus therapy in Japan: progress in clinical trials and future perspectives.
Japanese journal of clinical oncology, 2018Co-Authors: Satoru Taguchi, Hiroshi Fukuhara, Tomoki TodoAbstract:Oncolytic virus therapy is a promising new option for cancer. It utilizes genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming normal cells. T-VEC (talimogene laherparepvec), a second-generation Oncolytic herpes simplex virus type 1, was approved by the US Food and Drug Administration for the treatment of inoperable melanoma in 2015 and subsequently approved in Europe in 2016. Other Oncolytic viruses using different parental viruses have also been tested in Phase III clinical trials and are ready for drug approval: Pexa-Vec (pexastimogene devacirepvec), an Oncolytic vaccinia virus, CG0070, an Oncolytic adenovirus, and REOLYSIN (pelareorep), an Oncolytic reovirus. In Japan, as of May 2018, several Oncolytic viruses have been developed, and some have already proceeded to clinical trials. In this review, we summarize clinical trials assessing Oncolytic virus therapy that were conducted or are currently ongoing in Japan, specifically, T-VEC, the abovementioned Oncolytic herpes simplex virus type 1, G47Δ, a third-generation Oncolytic herpes simplex virus type 1, HF10, a naturally attenuated Oncolytic herpes simplex virus type 1, Telomelysin, an Oncolytic adenovirus, Surv.m-CRA, another Oncolytic adenovirus, and Sendai virus particle. In the near future, Oncolytic virus therapy may become an important and major treatment option for cancer in Japan.
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Oncolytic virus therapy: A new era of cancer treatment at dawn
Cancer science, 2016Co-Authors: Hiroshi Fukuhara, Yasushi Ino, Tomoki TodoAbstract: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.
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Oncolytic virus therapy for malignant brain tumors
Brain and nerve = Shinkei kenkyu no shinpo, 2009Co-Authors: Yasushi Ino, Tomoki TodoAbstract:Oncolytic viruses are genetically engineered, recombinant viruses or naturally occurring, attenuated viruses that infect, replicate selectively within, and destroy tumor cells. These viruses are nontoxic to normal tissues, and progeny viruses released from destroyed tumor cells can spread and infect surrounding tumor cells. In addition, most Oncolytic viruses can elicit specific antitumor immunity in the course of tumor cell destruction. Currently, the main route of virus administration is direct intratumoral injection that enables maximum virus delivery to tumor cells and minimum systemic adverse events. Several types of Oncolytic viruses have been tested in clinical trials for recurrent malignant glioma, among which genetically engineered herpes simplex viruses type 1 seems to be the most promising because of its high tumor selectivity (indicating safety) and potency (indicating efficacy). Oncolytic virus therapy has been developed for various types of cancers other than glioma, including malignant melanoma and prostate, breast, head & neck and colon cancers. Thus far, Oncolytic viruses that are inoculated intratumorally, are shown to be safe; adverse events typically observed are usually transient and include local inflammation and flu-like symptoms. Oncolytic viruses can be used in combination with chemotherapy or other conventional therapies, which, in some cases, can lead to synergistic effects. This review summarizes the recent advances in clinical and preclinical research on Oncolytic virus therapy for malignant brain tumors.
Lorenzo Galluzzi - One of the best experts on this subject based on the ideXlab platform.
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Trial Watch-Oncolytic viruses and cancer therapy.
Oncoimmunology, 2015Co-Authors: Erika Vacchelli, Alexander M.m. Eggermont, Catherine Sautès-fridman, Jérôme Galon, Laurence Zitvogel, Guido Kroemer, Lorenzo GalluzziAbstract:Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ Oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of Oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when Oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that Oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of Oncolytic virotherapy, especially when implemented in the absence of immunostimulatory interventions, remains unclear. Here, we cover the latest advances in this active area of translational investigation, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have been initiated in the same period to assess the therapeutic potential of Oncolytic virotherapy in oncological indications.
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Trial watch: Oncolytic viruses for cancer therapy.
Oncoimmunology, 2013Co-Authors: Erika Vacchelli, Catherine Sautès-fridman, Jérôme Galon, Laurence Zitvogel, Guido Kroemer, Alexander Eggermont, Lorenzo GalluzziAbstract:Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term "Oncolytic viruses" is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, Oncolytic viruses differ from so-called "oncotropic viruses" in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several different steps of the viral cycle, including the entry of virions (transductional specificity) as well as their intracellular survival and replication (post-transcriptional and transcriptional specificity). During the past two decades, a large array of replication-competent and replication-incompetent Oncolytic viruses has been developed and engineered to express gene products that would specifically promote the death of infected (cancer) cells. However, contrarily to long-standing beliefs, the antineoplastic activity of Oncolytic viruses is not a mere consequence of the cytopathic effect, i.e., the lethal outcome of an intense, productive viral infection, but rather involves the elicitation of an antitumor immune response. In line with this notion, Oncolytic viruses genetically modified to drive the local production of immunostimulatory cytokines exert more robust therapeutic effects than their non-engineered counterparts. Moreover, the efficacy of Oncolytic virotherapy is significantly improved by some extent of initial immunosuppression (facilitating viral replication and spread) followed by the administration of immunostimulatory molecules (boosting antitumor immune responses). In this Trial Watch, we will discuss the results of recent clinical trials that have evaluated/are evaluating the safety and antineoplastic potential of Oncolytic virotherapy.
Jonathan Pol - One of the best experts on this subject based on the ideXlab platform.
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Trial Watch: Oncolytic viro-immunotherapy of hematologic and solid tumors
OncoImmunology, 2018Co-Authors: Jonathan Pol, Sarah Levesque, Samuel Workenhe, Shashi Gujar, Fabrice Le Boeuf, Derek Clements, Jean-eudes Fahrner, Laetitia Fend, John Bell, Karen MossmanAbstract:Oncolytic viruses selectively target and kill cancer cells in an immunogenic fashion, thus supporting the establishment of therapeutically relevant tumor-specific immune responses. In 2015, the US Food and Drug Administration (FDA) approved the Oncolytic herpes simplex virus T-VEC for use in advanced melanoma patients. Since then, a plethora of trials has been initiated to assess the safety and efficacy of multiple Oncolytic viruses in patients affected with various malignancies. Here, we summarize recent preclinical and clinical progress in the field of Oncolytic virotherapy.
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Trial Watch-Oncolytic viruses and cancer therapy.
Oncoimmunology, 2015Co-Authors: Jonathan Pol, Jérôme Galon, Norma Bloy, Alexander Eggermont, Isabelle Cremer, Philippe Erbs, Aitziber Buqué, Fernando Aranda, Jitka Fucikova, Jean-marc LimacherAbstract:Oncolytic virotherapy relies on the administration of non-pathogenic viral strains that selectively infect and kill malignant cells while favoring the elicitation of a therapeutically relevant tumor-targeting immune response. During the past few years, great efforts have been dedicated to the development of Oncolytic viruses with improved specificity and potency. Such an intense wave of investigation has culminated this year in the regulatory approval by the US Food and Drug Administration (FDA) of a genetically engineered Oncolytic viral strain for use in melanoma patients. Here, we summarize recent preclinical and clinical advances in Oncolytic virotherapy.
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Trial Watch:: Oncolytic viruses for cancer therapy.
Oncoimmunology, 2014Co-Authors: Jonathan Pol, Jérôme Galon, Norma Bloy, Florine Obrist, Alexander Eggermont, Isabelle Cremer, Philippe Erbs, Jean-marc Limacher, Xavier Preville, Laurence ZitvogelAbstract:Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ Oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of Oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when Oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that Oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of Oncolytic virotherapy, especially when implemented in the absence of immunostimulatory interventions, remains unclear. Here, we cover the latest advances in this active area of translational investigation, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have been initiated in the same period to assess the therapeutic potential of Oncolytic virotherapy in oncological indications.
Jérôme Galon - One of the best experts on this subject based on the ideXlab platform.
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Trial Watch-Oncolytic viruses and cancer therapy.
Oncoimmunology, 2015Co-Authors: Erika Vacchelli, Alexander M.m. Eggermont, Catherine Sautès-fridman, Jérôme Galon, Laurence Zitvogel, Guido Kroemer, Lorenzo GalluzziAbstract:Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ Oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of Oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when Oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that Oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of Oncolytic virotherapy, especially when implemented in the absence of immunostimulatory interventions, remains unclear. Here, we cover the latest advances in this active area of translational investigation, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have been initiated in the same period to assess the therapeutic potential of Oncolytic virotherapy in oncological indications.
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Trial Watch-Oncolytic viruses and cancer therapy.
Oncoimmunology, 2015Co-Authors: Jonathan Pol, Jérôme Galon, Norma Bloy, Alexander Eggermont, Isabelle Cremer, Philippe Erbs, Aitziber Buqué, Fernando Aranda, Jitka Fucikova, Jean-marc LimacherAbstract:Oncolytic virotherapy relies on the administration of non-pathogenic viral strains that selectively infect and kill malignant cells while favoring the elicitation of a therapeutically relevant tumor-targeting immune response. During the past few years, great efforts have been dedicated to the development of Oncolytic viruses with improved specificity and potency. Such an intense wave of investigation has culminated this year in the regulatory approval by the US Food and Drug Administration (FDA) of a genetically engineered Oncolytic viral strain for use in melanoma patients. Here, we summarize recent preclinical and clinical advances in Oncolytic virotherapy.
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Trial Watch:: Oncolytic viruses for cancer therapy.
Oncoimmunology, 2014Co-Authors: Jonathan Pol, Jérôme Galon, Norma Bloy, Florine Obrist, Alexander Eggermont, Isabelle Cremer, Philippe Erbs, Jean-marc Limacher, Xavier Preville, Laurence ZitvogelAbstract:Oncolytic viruses are natural or genetically modified viral species that selectively infect and kill neoplastic cells. Such an innate or exogenously conferred specificity has generated considerable interest around the possibility to employ Oncolytic viruses as highly targeted agents that would mediate cancer cell-autonomous anticancer effects. Accumulating evidence, however, suggests that the therapeutic potential of Oncolytic virotherapy is not a simple consequence of the cytopathic effect, but strongly relies on the induction of an endogenous immune response against transformed cells. In line with this notion, superior anticancer effects are being observed when Oncolytic viruses are engineered to express (or co-administered with) immunostimulatory molecules. Although multiple studies have shown that Oncolytic viruses are well tolerated by cancer patients, the full-blown therapeutic potential of Oncolytic virotherapy, especially when implemented in the absence of immunostimulatory interventions, remains unclear. Here, we cover the latest advances in this active area of translational investigation, summarizing high-impact studies that have been published during the last 12 months and discussing clinical trials that have been initiated in the same period to assess the therapeutic potential of Oncolytic virotherapy in oncological indications.
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Trial watch: Oncolytic viruses for cancer therapy.
Oncoimmunology, 2013Co-Authors: Erika Vacchelli, Catherine Sautès-fridman, Jérôme Galon, Laurence Zitvogel, Guido Kroemer, Alexander Eggermont, Lorenzo GalluzziAbstract:Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term "Oncolytic viruses" is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, Oncolytic viruses differ from so-called "oncotropic viruses" in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several different steps of the viral cycle, including the entry of virions (transductional specificity) as well as their intracellular survival and replication (post-transcriptional and transcriptional specificity). During the past two decades, a large array of replication-competent and replication-incompetent Oncolytic viruses has been developed and engineered to express gene products that would specifically promote the death of infected (cancer) cells. However, contrarily to long-standing beliefs, the antineoplastic activity of Oncolytic viruses is not a mere consequence of the cytopathic effect, i.e., the lethal outcome of an intense, productive viral infection, but rather involves the elicitation of an antitumor immune response. In line with this notion, Oncolytic viruses genetically modified to drive the local production of immunostimulatory cytokines exert more robust therapeutic effects than their non-engineered counterparts. Moreover, the efficacy of Oncolytic virotherapy is significantly improved by some extent of initial immunosuppression (facilitating viral replication and spread) followed by the administration of immunostimulatory molecules (boosting antitumor immune responses). In this Trial Watch, we will discuss the results of recent clinical trials that have evaluated/are evaluating the safety and antineoplastic potential of Oncolytic virotherapy.
