Pexavec pexastimogene devacirepvec, an oncolytic vaccinia virus, cg0070, an oncolytic adenovirus, and reolysin pelareorep, an oncolytic reovirus. Combination of paclitaxel and mg1 oncolytic virus as a. Other oncolytic viruses using different parental viruses have also been tested in phase iii clinical trials and are ready for drug approval. Multimodal immunogenic cell death icd together with autophagy often induced by ovs not only presents potent danger signals to dendritic cells but also. Systemic spread as free virus particles or as virusinfected migratory cells occurs. Oncolytic viruses are a promising anticancer platform, achieving significant preclinical and clinical milestones in recent years. The use of oncolytic viruses is a new cancer treatment that is excellent at achieving just that. These viruses are capable of attacking cancer cells in a distinctive manner leading to cellspecific and targeted tumor therapy. Oncolytic viruses ovs are tumorselective, multimechanistic antitumor agents. The first generation of oncolytic adenovirus, onyx015 also known as dl 1520, h101 in china, is a genetically modified adenovirus with deletion of the 55 kd gene in the e1b region. Oncolytic viruses are native or attenuated viruses that selectively replicate in cancer cells and induce host antitumor immunity. Tvec is an oncolytic virus, a virus that selectively replicates inside and kills cancer cells.
This diversity of virotherapeutics not only offers interesting opportunities for the. Vesicular stomatitis virus has extensive oncolytic activity against human sarcomas. In the last two decades, different oncolytic viruses ovs have been modified and tested in a number of preclinical studies, some of which have led to clinical trials in cancer patients. Jun 19, 2015 some viruses can infect cancer cells specifically, and cause them to burst. M, have proven also to be efficient carriers for oncolytic adenovirus. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells. An oncolytic virus is a virus that preferentially infects and kills cancer cells. An oncolytic virus named imlygictm manufactured by amgen recently received the stamp of approval from. Nevertheless, despite extensive research, oncolytic virotherapy has shown limited efficacy against solid tumors. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. T1 genetic engineering of oncolytic viruses for cancer therapy. Oncolytic viruses as engineering platforms for combination. The use of replicationcompetent viruses as oncolytic agents is rapidly expanding, with several oncolytic viruses approved for cancer therapy.
Oncolytic virus therapy free download as powerpoint presentation. Oral viral vaccines are suitable for poliovirus, rotavirus, rabies virus, typhoid virus, etc. This therapy takes advantage of the natural propensity of most tumor cells to be infected by specific ovs. Methods and protocols aims to ensure successful results in the further study of this vital field. Cell free therapy is an alternative to cellbased therapy, which is. Dec 12, 2016 pioneers in oncolytic virus and gene therapy fields announce formation of ignite immunotherapy inc. Recent advances in viral retargeting, genetic editing.
Some viruses can infect cancer cells specifically, and cause them to burst. Pdf since the turn of the nineteenth century, when their existence was first recognized. Although mathematical models have been developed to understand the dynamics of tumor virotherapy, a. May 15, 2017 the concept of oncolytic virus ovmediated cancer therapy has been shifted from an operational virotherapy paradigm to an immunotherapy.
Pioneers in oncolytic virus and gene therapy fields announce formation of ignite immunotherapy inc. Oncolytic viruses can occur naturally or can be made in the laboratory by changing other viruses. Genetic engineering of oncolytic viruses for cancer therapy. Oncolytic virotherapy is an exciting, increasingly recognized discipline in cancer research. Both these ovs are restricted to intratumoral administration into cancer lesions. To quantitatively understand the systematic behavior of oncolytic virotherapy that contains complicated feedback regulations and elucidate the influence of the amount of viruses and immune.
Studies proving the ability of oncolytic viruses ovs to target and rapidly kill cancer cells have led to approval of h101 and imlygic. We and others have developed a number of strategies to further stimulate antitumor immunity and to. Oncolytic viruses ovs selectively replicate in and kill cancer cells, and. With the first ov talimogene laherparepvec tvec obtaining us food and drug administration approval, interest in ovs has been boosted greatly. Oncolytic viruses are a promising class of antitumor agents. Rare resistance is overcome by blocking interferon pathways 6 july 2011 journal of virology, vol. Oncolytic virotherapy dove press open access publisher. They selectively infect and kill cancer cells while sparing the normal counterparts, expose cancer specific antigens and activate the host immune system against both viral and tumor determinants. Pioneers in oncolytic virus and gene therapy fields. Oncolytic virotherapy call for papers dove press open.
Oncolytic viruses are one of the most promising novel therapeutics for malignant cancers. Definition of oncolytic virus nci dictionary of cancer. On the basis of preliminary, and unpublished, results from these phase i trials, we predict that phase ii and phase iii trials will soon clarify the role of the host immune system in the antitumor effect. Some oncolytic viruses ovs have a natural preference for tumor cells such as coxsackie virus known to cause sores on the mouth and measles virus, whereas others have to be engineered to replicate specifically in cancer cells such as adenovirus ad and herpes simplex virus hsv. Many viruses are inactive as a result of the ph in the gastrointestinal tract and multiple enzymes. The potential of oncolytic viruses for treating cancer duration. Oncolytic viruses as therapeutic cancer vaccines molecular. Oncolytic virus therapy shows benefit in patients with. Scribd is the worlds largest social reading and publishing site. Methods and protocols describes the construction and purification of capsidmodified adenoviruses as well as oncolytic adenoviruses, presents protocols for many individual virus species including engineering and preparation of oncolytic hsv, propagation, purification, and in vivo testing of oncolytic vsv, details properties. Oncolytic viruses ovs constitute a new and promising immunotherapeutic approach toward cancer treatment. Apr 25, 2018 in this opinion article, twumasiboateng et al. Vec has completed phase iii clinical trials in advanced melanoma patients and achieved significant therapeutic effects. Oncolytic viruses ovs are powerful new therapeutic agents in cancer therapy.
Oncolytic viruses represent a new class of therapeutic agents that promote antitumour responses through a dual mechanism of action that is dependent on selective tumour cell killing and the induction of systemic antitumour immunity. Certain oncolytic viruses are being studied in the treatment of cancer. Current status of clinical trials assessing oncolytic virus. Oncolytic definition and meaning collins english dictionary. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host. Secondgeneration oncolytic viruses, including delta24rgd and icovir, have also reached the clinical setting for a variety of cancers. Oncolytic adenovirus was one of the first oncolytic viruses to be developed and licensed for treatment of cancer 8, 24. In this report, we demonstrate the compatibility of oncolytic virotherapy and chemotherapy using various murine breast cancer models. They may make it easier to kill tumor cells with chemotherapy and radiation therapy. Oncolytic viruses directly lyse tumour cells, leading to.
A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. Cancer cellderived evs transporting oncolytic adenovirus ad5d24 exhibited a tumorselective delivery in a lung carcinoma model. Oncolytic viruses are a novel class of anticancer agents which in many cases have entered clinical trials. Oncolytic viruses ovs, evolved and engineered for cancer. An evolving new field in clinical oncology is the application of conditionally replicating viruses that selectively destroy tumor cells, so called oncolytic viruses 1,2,3, 4. Oncolytic viruses are replicating microorganisms that have been selected or engineered to grow inside tumor cells. Since the first report of an engineered oncolytic virus, there has been a. Oncolytic adenovirus programmed by synthetic gene circuit. Oncolytic adenovirus an overview sciencedirect topics. Updates to the antitumor mechanism of oncolytic virus. The potential of oncolytic viruses for treating cancer. Il12 is a potent anticancer agent that promotes thelper 1 th1. As responses to therapy are highly variable, understanding the dynamics of therapy is critical for optimal application of virotherapy in practice. In vivo estimation of oncolytic virus populations within.
Oncolytic viruses ovs target and destroy cancer cells while sparing their normal counterparts. Ovs often induce immunogenic cell death icd of cancer cells, and they may interact directly with immune cells as well to prime antitumor immunity. Viruses free fulltext overcoming barriers in oncolytic. Integrating oncolytic viruses in combination cancer. The current study describes oncolytic mv production in vero cells grown on microcarrier using serum. A full arsenal of selective, safe, and effective viruses has been developed with some emerging preclinical research focusing on optimizing these therapies in the face of remaining challenges, both in the. Cells free fulltext oncolytic virus encoding a master.
Clinicaltrials in oncology have been performed with oncolytic viruses. Although the connection between viruses and cancer regression was recognized in the early 20th century, it wasnt until the recent development of advanced genetic engineering techniques that true progress has been made using virotherapy to attack and destroy cancer cells. These viruses have been evaluated in numerous studies at both preclinical and clinical levels and the recent food and drug administration fda approval of an oncolytic herpesvirusbased treatment raises optimism that ovs will become a therapeutic option for cancer patients. Pdf oncolytic viruses represent a new class of therapeutic agents that promote antitumour responses through a dual mechanism of action that is. Here, examination of early oncolytic virotherapy before genetic engineering serves to. This carries serious implications in terms of toxicities for patients, feasibility for care providers and costs for healthcare systems. Jci unleashing the therapeutic potential of oncolytic viruses. Pdf viruses capable of inducing lysis of malignant cells through. Herpes simplex virus type 1 has strong lytic properties and several variants have been constructed, often via deletion of the icp34. A type of virus that infects and lyses breaks down cancer cells but not normal cells. Oncolytic viruses ovs are genetically modified or naturally occurring viruses, which preferentially replicate in and kill cancer cells while sparing healthy cells, and induce antitumor immunity.
Jcm free fulltext oncolytic virotherapy with myxoma virus. On the other hand, optimization of serumfree culture conditions, increasing virus yields, development of scalable purification strategies, and formulations. Oncolytic virus therapy has recently been recognized as a promising new option for the treatment of cancer. Oncolytic virus ov therapy is based on selective replication of viruses in. Many types of viruses have been tested as potential oncolytic viruses, including herpesvirus, poxvirus, picornavirus e. This particular oncolytic virus is based on herpes simplex virus type 1 and has been modified to include a gene that codes for gmcsf, a protein that stimulates the production of immune cells in the body. Oncolytic viruses range in size and complexity from large, doublestranded dna viruses such as vaccinia 190 kilobase kb 17 and hsv1 152 kb 18 to the tiny parvovirus h1 5kb linear, singlestranded dna. They kill infected cancer and associated endothelial cells via direct oncolysis, and uninfected cells via tumor vasculature targeting and bystander effect. The use of oncolytic viruses is a promising approach for the treatment of disseminated diseases like breast cancer, with the first candidate recently approved by the food and drug administration for use in patients. Oncolytic virotherapy ovt is a promising approach in which wt or engineered viruses selectively replicate and destroy tumor cells while sparing normal ones. Ovinduced tumor immunity can be enhanced through viral expression of antitumor cytokines such as interleukin 12 il12. Oncolytic viruses can be used as monotherapy or combined with existing cancer therapies to become more potent.
Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancerimmunity cycle. Oncolytic viruses ovs are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. However, the clinical translation of this therapy concept has one major hurdle. Vesicular stomatitis virus as an oncolytic vector viral. Oncolytic viruses ovs are a versatile new class of therapeutic agents based on native or genetically modified viruses that selectively replicate in tumor cells and can express therapeutic transgenes designed to target cells within the tumor microenvironment andor host immunity. Oncolytic measles viruses produced at different scales under. Oncolytic viruses and their application to cancer immunotherapy. The publishers final edited version of this article is available free at cancer immunol res. One promising oncolytic virus therapy is called tvec, and is currently in late. Oncolytic virotherapy is a selective and powerful tool for cancer treatment. The engineering involves replacing the native thymidine kinase vvtk gene, in a wyeth strain vaccinia backbone, with the herpes simplex virus thymidine kinase hsvtk gene, which. Although oncolytic viruses range from natural without modifications to genetically engineered viruses, a. Pioneers in oncolytic virus and gene therapy fields announce.