scholarly journals To Infection and Beyond: The Multi-Pronged Anti-Cancer Mechanisms of Oncolytic Viruses

Viruses ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 43 ◽  
Author(s):  
Kevin Cassady ◽  
Kellie Haworth ◽  
Josh Jackson ◽  
James Markert ◽  
Timothy Cripe
Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3327
Author(s):  
Tabitha G. Cunliffe ◽  
Emily A. Bates ◽  
Alan L. Parker

More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, although immunologically “cold” tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus, have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergise with immunotherapies by turning immunologically “cold” tumours “hot”. Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective “precision virotherapies” that are extensively engineered to prevent off-target up take via native routes of infection and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field.


2020 ◽  
Author(s):  
Anjali Lathwal ◽  
Rajesh Kumar ◽  
Gajendra P.S. Raghava

AbstractOne of the emerging technologies to fight against cancer is oncolytic virus-based immunotherapy which directly lysis tumor cells. Recently, the FDA approved an oncolytic virus named T-vec for the treatment of melanoma; several hundred other viruses are in clinical trials. In order to facilitate the scientific community to fight against cancer, we build a repository of oncolytic viruses called OvirusTdb (https://webs.iiitd.edu.in/raghava/ovirustdb/). This is a manually curated repository where information is curated from research papers and patents. The current version of the repository maintains comprehensive information on therapeutically important oncolytic viruses with 5927 records where each record has 25 fields such as the virus species, cancer cell line, synergism with anti-cancer drugs, and many more. It stores information on 09 types of DNA and 15 types of RNA viruses; 300 recombinant and 09 wildtype viral strains; tested against 124 cancer types and 427 cancer cell lines. Approximately, 1047 records show improved anti-cancer response using combinatorial approach of chemotherapeutic agents with virus strains. Nearly, 3243 and 1506 records show cancer cell death via apoptosis induction and immune activation, respectively. In summary, a user-friendly web repository of oncolytic viruses for information retrieval and analysis have been developed to facilitate researchers in designing and discovering new oncolytic viruses for effective cancer treatment.


2008 ◽  
Vol 2 ◽  
pp. CMO.S416 ◽  
Author(s):  
Robin J Prestwich ◽  
Fiona Errington ◽  
Kevin J. Harrington ◽  
Hardev S. Pandha ◽  
Peter Selby ◽  
...  

Oncolytic viruses are replication competent, tumor selective and lyse cancer cells. Their potential for anti-cancer therapy is based upon the concept that selective intratumoral replication will produce a potent anti-tumor effect and possibly bystander or remote cell killing, whilst minimizing normal tissue toxicity. Viruses may be naturally oncolytic or be engineered for oncolytic activity, and possess a host of different mechanisms to provide tumor selectivity. Clinical use of live replicating viruses is associated with a unique set of safety issues. Clinical experience has so far provided evidence of limited efficacy and a favourable toxicity profile. The interaction with the host immune system is complex. An anti-viral immune response may limit efficacy by rapidly clearing the virus. However, virally-induced cell lysis releases tumor associated antigens in a ‘dangerous’ context, and limited evidence suggests that this can lead to the generation of a specific anti-tumor immune response. Combination therapy with chemotherapy or radiotherapy represents a promising avenue for ongoing translation of oncolytic viruses into clinical practice. Obstacles to therapy include highly effective non-specific host mechanisms to clear virus following systemic delivery, immune-mediated clearance, and intratumoral barriers limiting virus spread. A number of novel strategies are now under investigation to overcome these barriers. This review provides an overview of the potential role of oncolytic viruses, highlighting recent progress towards developing effective therapy and asks if they are a realistic therapeutic option at this stage.


Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 94 ◽  
Author(s):  
Daria Chulpanova ◽  
Valeriya Solovyeva ◽  
Kristina Kitaeva ◽  
Stephen Dunham ◽  
Svetlana Khaiboullina ◽  
...  

Recombinant viruses are novel therapeutic agents that can be utilized for treatment of various diseases, including cancers. Recombinant viruses can be engineered to express foreign transgenes and have a broad tropism allowing gene expression in a wide range of host cells. They can be selected or designed for specific therapeutic goals; for example, recombinant viruses could be used to stimulate host immune response against tumor-specific antigens and therefore overcome the ability of the tumor to evade the host’s immune surveillance. Alternatively, recombinant viruses could express immunomodulatory genes which stimulate an anti-cancer immune response. Oncolytic viruses can replicate specifically in tumor cells and induce toxic effects leading to cell lysis and apoptosis. However, each of these approaches face certain difficulties that must be resolved to achieve maximum therapeutic efficacy. In this review we discuss actively developing approaches for cancer therapy based on recombinant viruses, problems that need to be overcome, and possible prospects for further development of recombinant virus based therapy.


2019 ◽  
Vol 73 ◽  
pp. 898-908
Author(s):  
Zuzanna Rzepka ◽  
Marta Knapik ◽  
Dorota Wrześniok

Cancers are a significant health problem in the world. The most common therapeutic methods applied in oncology are chemotherapy, radiotherapy and surgical methods. Finding new therapies in this branch of medicine, as well as developing solutions with the highest possible effectiveness, taking into account the multifactorial nature of cancer, is important from both the scientific and medical point of view and, for obvious reasons, it is in the interest of many people. Immunotherapy, despite many years of initial failures, has become one of the most important clinically approved new treatments in oncology and is now successfully used in the treatment of certain types of cancer. Current immunotherapeutic strategies are based on monoclonal antibodies (including inhibitors of immune control points), cytokines, anti-cancer vaccines, oncolytic viruses, as well as adoptive cell transfer. For many cancer immunotherapies, an increase in their effectiveness is observed when they are used with other types of immunotherapy as well as in combination with molecular targeted therapy, chemotherapy or radiotherapy. The dynamic development of cancer immunotherapy since the beginning of the 21st century results from the advances in genetic engineering, as well as from the increase in knowledge about the anticancer immune response and the nature of cancer cells including abnormalities in their metabolism, the ability to create a tumor microenvironment and the induction of immunosuppression. The aim of the study is to present current knowledge in the field of cancer immunotherapy strategies.


Biomedicines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 104 ◽  
Author(s):  
Christopher LaRocca ◽  
Susanne Warner

Oncolytic viruses have emerged as a novel class of anti-cancer therapeutics with one virus already receiving United States Food and Drug Administration (FDA) approval (talimogene laherparepvec) and many others undergoing testing in clinical trials. These viruses have direct lytic effects on tumor cells as well as immunomodulatory functions to increase inflammatory cell infiltrates in the tumor microenvironment. Despite all of the advances in cancer care, pancreatic cancer remains a highly lethal malignancy. One of the main barriers to successful systemic treatment of the disease is the fibrotic tumor stroma, as the unique extracellular matrix creates an environment that promotes tumor growth and is resistant to chemotherapy and other anti-cancer agents. The pleiotropic effects of Vitamin D have been widely studied, but recent research has now demonstrated it to be an effective agent in modulating pancreatic cancer stroma to facilitate the enhanced delivery of cytotoxic chemotherapy and immunogenicity in response to treatment. This review will explore the combination of Vitamin D with oncolytic viruses and how this novel application of Vitamin D’s ability to modulate pancreatic tumor stroma may result in a potential mechanism for increasing the efficacy of oncolytic virotherapy in pancreatic cancer.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3057
Author(s):  
Lukasz Kuryk ◽  
Laura Bertinato ◽  
Monika Staniszewska ◽  
Katarzyna Pancer ◽  
Magdalena Wieczorek ◽  
...  

In this review, we discuss the use of oncolytic viruses and checkpoint inhibitors in cancer immunotherapy in melanoma, with a particular focus on combinatory therapies. Oncolytic viruses are promising and novel anti-cancer agents, currently under investigation in many clinical trials both as monotherapy and in combination with other therapeutics. They have shown the ability to exhibit synergistic anticancer activity with checkpoint inhibitors, chemotherapy, radiotherapy. A coupling between oncolytic viruses and checkpoint inhibitors is a well-accepted strategy for future cancer therapies. However, eradicating advanced cancers and tailoring the immune response for complete tumor clearance is an ongoing problem. Despite current advances in cancer research, monotherapy has shown limited efficacy against solid tumors. Therefore, current improvements in virus targeting, genetic modification, enhanced immunogenicity, improved oncolytic properties and combination strategies have a potential to widen the applications of immuno-oncology (IO) in cancer treatment. Here, we summarize the strategy of combinatory therapy with an oncolytic vector to combat melanoma and highlight the need to optimize current practices and improve clinical outcomes.


Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 204 ◽  
Author(s):  
Zong Sheng Guo ◽  
Michael T. Lotze ◽  
Zhi Zhu ◽  
Walter J. Storkus ◽  
Xiao-Tong Song

Oncolytic viruses (OVs) are potent anti-cancer biologics with a bright future, having substantial evidence of efficacy in patients with cancer. Bi- and tri-specific antibodies targeting tumor antigens and capable of activating T cell receptor signaling have also shown great promise in cancer immunotherapy. In a cutting-edge strategy, investigators have incorporated the two independent anti-cancer modalities, transforming them into bi- or tri-specific T cell engager (BiTE or TriTE)-armed OVs for targeted immunotherapy. Since 2014, multiple research teams have studied this combinatorial strategy, and it showed substantial efficacy in various tumor models. Here, we first provide a brief overview of the current status of oncolytic virotherapy and the use of multi-specific antibodies for cancer immunotherapy. We then summarize progress on BiTE and TriTE antibodies as a novel class of cancer therapeutics in preclinical and clinical studies, followed by a discussion of BiTE- or TriTE-armed OVs for cancer therapy in translational models. In addition, T cell receptor mimics (TCRm) have been developed into BiTEs and are expected to greatly expand the application of BiTEs and BiTE-armed OVs for the effective targeting of intracellular tumor antigens. Future applications of such innovative combination strategies are emerging as precision cancer immunotherapies.


Author(s):  
Tabitha G. Cunliffe ◽  
Emily A. Bates ◽  
Alan L. Parker

More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, though immunologically “cold” tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergize with immunotherapies by turning immunologically “cold” tumours “hot”. Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective “precision virotherapies” that are extensively engineered to prevent off-target up take via native routes of infection, and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field.


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