Pdf perspectives on immunotherapy via oncolytic viruses. Jan 31, 2012 oncolytic adenovirus was one of the first oncolytic viruses to be developed and licensed for treatment of cancer 8, 24. Virotherapy is a novel treatment for cancer, which may be delivered as a single agent or in combination with other therapies. Oncolytic virus ov therapeutics are designed to rapidly and specifically grow in. Advances in the understanding of cancer immunotherapy and the development of multiple checkpoint inhibitors have dramatically changed the current landscape of cancer treatment. Retargeting of viruses to generate oncolytic agents. Oncolytic virus immunotherapy journal for immunotherapy of. Oncolytic virotherapy ovt is a promising approach in which wt or engineered viruses selectively replicate and destroy tumor cells while sparing normal ones. Ovs can revert cancerassociated immune suppression and initiate clinically meaningful antitumor immune responses. The approval of the first oncolytic virus ov for the treatment of metastatic melanoma and the recent discovery. These viruses do not simply lyse cells to achieve their cancer. Oncolytic virus and pd1pdl1 blockade combination therapy. Tumorselectively replicating oncolytic viruses are promising tools for therapy of solid cancers and have been initially developed to achieve potent tumor lysis with acceptable side effects on healthy tissue. 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.
As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host antitumour immune system responses. Cellular proteins released from the ovlysed tumor cells, known as damageassociated molecular patterns and tumorassociated antigens, activate dendritic cells and. All these therapeutic approaches fight systemic disease, be it micrometastatic. In 2006, the world witnessed the first governmentapproved oncolytic virus for the treatment of head and neck cancer. Oncolytic adenovirusmediated therapy for prostate cancer. Evaluation of oncolytic virusinduced therapeutic tumor vaccination effects in murine tumor models. Pdf oncolytic viruses have primarily the unique advantage in the fact that they can only infect and destroy cancer cells. Jun 01, 2017 oncolytic viruses offer the attractive therapeutic combination of tumorspecific cell lysis together with immune stimulation, therefore acting as potential in situ tumor vaccines.
It represents a unique class of cancer therapeutics with distinct mechanisms of action. Oncolytic viruses offer a rational alternative to solve the limitations of those immunotherapies, but the lack of headtohead comparisons between different virus platforms has slowed optimization of the approach. Moreover, ovs can be engineered for optimization of tumor selectivity and enhanced immune stimulation and can be readily combined with other agents. Shanghai sunway biotech expects to begin marketing h101 in july for treating head and neck cancer. The oncolytic virus induced the infiltration of immune cells known as t cells into tumors that had low levels of these cells prior to treatment, the researchers found the study suggests that the viral therapy can change the local microenvironment to make an immunologically cold tumor. Oncolytic viruses especially properly armed ones have positive effects on almost every aspect of the cancerimmunity cycle and can change the cancerimmune set point. Incorporation of microrna target sequences can be used to control exogenous gene expression and viral tropism in specific tissues to enhance the therapeutic indices of oncolytic viruses expressing therapeutic transgenes. Oncolytic viruses as therapeutic cancer vaccines roswell park. Oncolytic virotherapy dove press open access publisher. Recent clinical success has demonstrated the great potential of cancer immunotherapy to overcome tumormediated immunosuppression.
There is currently one oncolytic virus therapy approved by the fda for the treatment of cancer. Research studies indicated that the combination of viral therapy and radiation therapy has synergistic antitumor effects in in vitro and in vivo. Pdf oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in. Oncolytic virotherapy is an emerging therapeutic for the treatment of cancer that exploits replicationcompetent viruses to selectively infect and destroy cancerous cells while sparing normal cells and tissues. Jci unleashing the therapeutic potential of oncolytic viruses. Targeted therapy of cancer using oncolytic viruses has generated much interest over the past few years in the light of the limited efficacy and side effects of standard cancer therapeutics for advanced disease. 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. Aug 30, 2016 combining oncolytic viruses with cancer immunotherapy. Phocus, optim are establishing use of oncolytic viruses as another tool in the cancer therapeutics armamentarium. Here, we report mesenchymal stem cells mscs as a carrier for the delivery of oncolytic newcastle disease virus ndv for the treatment of hpvassociated tumor.
Oncolytic virotherapy is a promising form of gene therapy for cancer, employing natures own agents to find and destroy malignant cells. Oncolytic virotherapy is an approach that uses oncolytic viruses ovs, either with natural tropism for neoplastic cells or genetically modified to enhance selectivity for tumor cells. Oncolytic viruses and their application to cancer immunotherapy. 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. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a. Pdf oncolytic virusesnatural and genetically engineered. Currently, cancer immunotherapy interventions focus on mitigating tumor associated immune evasion wei et al.
Oncolytic viruses ovs preferentially infect and lyse transformed cells, leaving normal cells relatively unharmed. When under control of many types of oncolytic virus, the cells resources are diverted away from cellular activities into a. To integrate the oncolytic adenovirusbased gene therapy and the i1mabbased radioimmunotherapy, this study combined the carg element of. Oncolytic viruses directly lyse tumour cells, leading to.
Human papillomavirus hpvassociated malignancy remain a main cause of cancer in men and women. Several studies in prostate cancer models demonstrate excellent efficacy with oncolytic viruses, both promoterdriven and complementation mutants, expressing gmcsf or interleukins il12, il24, cd40l, and flt3l. Jan 14, 2016 oncolytic viruses can be found at the confluence of virology, genetic engineering and pharmacology where versatile platforms for molecularly targeted anticancer agents can be designed and optimised. Human mesenchymal stromal cells deliver systemic oncolytic. Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells 22. Immune checkpoint blockade is arguably the most effective current cancer therapy approach. Lately, engineered oncolytic viruses have been shown to be effective for local and systemic immunotherapies in cancer. Oncolytic activity of hf10 in head and neck squamous cell. Oncolytic virus ov therapy is based on selective replication of viruses in cancer cells and their subsequent spread within a tumor without causing damage to normal tissue 1, 2. Extended treatment with myneovax, personalized neoantigen. Smcs synergize with the attenuated oncolytic vesicular stomatitis virus vsv. Shedding studies for virus, bacteriabased gene therapy. Engeland editor this book aims to provide a guide for virologists, translational researchers, and clinicians in the field of cancer research by providing reference protocols and methodologies fr. This book aims to provide a guide for basic virologists, translational researchers and clinician scientists in the field by providing reference protocols from vector development to clinical translation.
Immunotherapy is at the forefront of modern oncologic care. However, in recent years, oncolytic viruses have been recognized as therapeutic vehicles exhibiting multipronged antitumoral activity. Oncolytic viruses are replicating microorganisms that have been selected or engineered to grow inside tumor cells. Background oncolytic viruses are cancer therapeutics based on viruses whose replication is restricted to malignant cells fig. They lack crossresistance with existing therapies, and the acceptable safety profile of ovs has been demonstrated in numerous trials. Oncolytic virus and pd1pdl1 blockade combination therapy chunyu chen,1 brian hutzen,1 mary f wedekind,1,2 timothy p cripe1,2 1department of pediatrics, center for childhood cancer and blood diseases, nationwide childrens hospital, 2division of hematologyoncologyblood and marrow transplantation, nationwide childrens hospital, the ohio state university, columbus, oh, usa. The concept of using viruses to treat cancer dates back over a century. Ovs and their resultant immunological events can act at both primary and metastatic sites. Comparison of clinically relevant oncolytic virus platforms.
Frontiers oncolytic viruses partner with tcell therapy. Cancer immunotherapy has represented great potential as a new promising cancer therapeutic approach. It has been known for many years that viruses have the ability to. This document describes the general principles for the manufacturing, characterisation, nonclinical and clinical testing of medicinal products based on oncolytic viruses keywords. Oncolytic virus is considered as a genetically built or naturally occurring virus that will kill the cancer cells without hurting the ordinary human tissues. A few years ago, the first oncolytic virus was approved by the fda for. Jan 18, 2016 by nishita parnandi figures by krissy lyon one of the biggest challenges in treating cancer is to specifically target the cancerous site in a tissue without killing the surrounding normal cells. Jun 06, 2012 oncolytic viruses, by definition, are viruses that are capable of infecting and selectively replicating in cancer cells, eventually leading to cell death without harming healthy cells.
In the second trial, which included 21 patients, tvec was combined with pembrolizumab keytruda. Sep 23, 20 clinical development of oncolytic virus therapy began over a century ago and, since then, numerous trials have been initiated to treat hundreds of cancer patients with a variety of native, modified, and recombinant oncolytic viruses. This document describes the general principles for the manufacturing, characterisation, nonclinical and clinical testing of medicinal products based on oncolytic viruses. Various novel therapies have targeted all three layers of tumor biology. Targeted therapies relate to small molecule inhibitors. Cancer vaccines and oncolytic viruses exert profoundly. Oncolytic viruses ovs preferentially infect and kill cancer cells without harming normal cells. Oncolytic viruses can be used as monotherapy or combined with existing cancer therapies to become more potent. Oncolytic viruses can kill tumour cells through a dual mechanism of action. Design and application of oncolytic viruses for cancer. Keywords virotherapy vector design immunomonitoring mathematical modeling talimogene laherparepvec clinical translation.
Genetically modified oncolytic viruses ovs kill tumor cells via completely unique mechanisms compared to small molecule chemotherapeutics. Genetic engineering of oncolytic viruses for cancer. Immunotherapies include checkpoint inhibitory antibodies, chimeric antigen receptor car tcells, cancer vaccines, and oncolytic viruses. While some viruses seem to have a natural preference for tumor cells, most viruses require the modification of their tropism to specifically enter and replicate in such cells. Gene therapy, oncolytic viruses, wild type, genetically modified oncolytic viruses, manufacture, characterisation, nonclinical, clinical, biosafety.
Current standard treatments of cancer can prolong survival of many cancer patients but usually do not effectively cure the disease. Oncolytic viruses, oncolytic viral vaccine, immunomodulatory oncolytic virus, tumor niche biology, cancer. Head and neck cancer, includes cancers of the mouth, nose, sinuses, ear, salivary glands. Oncolytic activity of hf10 in head and neck squamous cell carcinomas. They kill infected cancer and associated endothelial cells via. One emerging class in both primary and salvage therapy is oncolytic viruses. Understanding of viruses accelerated rapidly in the 1950s and 1960s, in large measure because of the advent of cell and tissue culture systems that allowed ex vivo virus propagation. Oncolytic newcastle disease virus expressing a checkpoint. Mar 01, 2006 oncolytic viruses are live viruses that selectively kill cancer cells. Micrornas regulate gene expression in mammalian cells and often exhibit tissuespecific expression patterns. Methods and protocols aims to ensure successful results in the further study of this vital field. Design and analysis of shedding studies for virus or bacteriabased gene therapy and oncolytic products guidance for industry august 2015 download the final guidance document read the federal. Thus, ovs can be exploited for cancer gene therapies and immunotherapies alone or in.
Tumor cells often lack an adequate antiviral response, making them more susceptible to ov infection than healthy cells. An oncolytic virus named imlygictm manufactured by amgen recently received the stamp of approval from. Perspectives on immunotherapy via oncolytic viruses. Oncolytic virus therapy is based on the ability of viruses to effectively infect and kill tumor cells without destroying the normal tissues. Cancer vaccines and oncolytic viruses exert profoundly lower. In this paper, we proposed two models in the form of partial differential equations to investigate the spatiotemporal. The use of oncolytic viruses is a new cancer treatment that is excellent at achieving just that. The approval of the first oncolytic virus ov for the treatment of metastatic melanoma. Smac mimetic compounds smcs are anticancer drugs that antagonize inhibitor of apoptosis proteins, which consequently sensitize cancer cells to death in the presence of proinflammatory ligands such as tumor necrosis factor alpha tnf. The ex vivo purge of cancer cells using oncolytic viruses. 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 comprise an emerging cancer therapeutic modality whose activity involves both direct tumor cell lysis and the induction of immunogenic cell death icd. Oncolytic viruses can be usefully integrated into tumour immunotherapies, as they target multiple steps within the cancerimmunity cycle. The ability of ovs to enter and destroy cancer cells was first proposed more than a century ago, but the therapeutic benefits of ovs in cancer patients have only been recently realized in clinical trials, with the help of.
The first oncolytic virus has been approved in china. Early stage clinical trials using oncolytic viruses show induction of effector anti tumor immune responses and suggest that such therapies could also morph and. Recent developments in cancer immunotherapy have generated renewed interest in oncolytic viruses as platforms for the. Oncolytic viruses ovs are tumorselective, multimechanistic antitumor agents. Modeling the spatiotemporal dynamics of oncolytic viruses. Clinicaltrials in oncology have been performed with oncolytic viruses fornearly fifty years. Written in the highly successful methods in molecular biology series format. Oncolytic virus therapy cancer research institute cri. An oncolytic virus is a virus that preferentially infects and kills cancer cells. The company is also testing the virus in lung cancer and has bought the rights to onyx15, an almost identical virus that onyx pharmaceuticals took into phase iii trials in. Viruses free fulltext oncolytic viruses for cancer.
In addition, given major differences in the biology of popular oncolytic viruses, there might be different optimal uses for each. 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. China approves worlds first oncolytic virus therapy for. The therapeutic efficacy of oncolytic viruses is built on the recruitment of t cells and the induction of tumorreactive immunity. Oncolytic viruses ovs have been selected or genetically engineered to preferentially infect, replicate in, and lyse tumor cells while sparing normal cells. Side effects may vary according to the type of oncolytic virus and what exactly it targetsand may also be influenced by. Integrating oncolytic viruses in combination cancer. The potential of the combined use of targeted type i. Oncolytic adenovirus programmed by synthetic gene circuit for.1134 130 524 295 293 1464 254 858 1200 772 435 77 822 1457 4 784 1322 451 833 244 281 1010 1411 871 1272 370 831 1180