scholarly journals Hitting the Target but Missing the Point: Recent Progress towards Adenovirus-Based Precision Virotherapies

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3327
Author(s):  
Tabitha G. Cunliffe ◽  
Emily A. Bates ◽  
Alan L. Parker
Keyword(s):  
Viral Genome ◽  
Recent Progress ◽  
Oncolytic Viruses ◽  
Transformed Cells ◽  
Immunogenic Cell Death ◽  
Full Potential ◽  
Immune Mediated ◽  
Efficacious Treatment ◽  
Anti Cancer ◽  
Improvement In Survival

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.

scholarly journals Hitting the Target but Missing the Point: Recent Progress Towards Adenovirus-Based Precision Virotherapies

2020 ◽  
Author(s):  
Tabitha G. Cunliffe ◽  
Emily A. Bates ◽  
Alan L. Parker
Keyword(s):  
Viral Genome ◽  
Recent Progress ◽  
Oncolytic Viruses ◽  
Transformed Cells ◽  
Immunogenic Cell Death ◽  
Full Potential ◽  
Immune Mediated ◽  
Efficacious Treatment ◽  
Anti Cancer ◽  
Improvement In Survival

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.

scholarly journals Hitting the Target but Missing the Point: Recent Progress Towards Adenovirus-Based Precision Virotherapies

2020 ◽  
Author(s):  
Tabitha G. Cunliffe ◽  
Emily A. Bates ◽  
Alan L. Parker
Keyword(s):  
Viral Genome ◽  
Recent Progress ◽  
Oncolytic Viruses ◽  
Transformed Cells ◽  
Immunogenic Cell Death ◽  
Full Potential ◽  
Immune Mediated ◽  
Efficacious Treatment ◽  
Anti Cancer ◽  
Improvement In Survival

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.

scholarly journals Oncolytic Viruses: Do They Have a Role in Anti-Cancer Therapy?

2008 ◽  
Vol 2 ◽  
pp. CMO.S416 ◽  
Author(s):  
Robin J Prestwich ◽  
Fiona Errington ◽  
Kevin J. Harrington ◽  
Hardev S. Pandha ◽  
Peter Selby ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Therapy ◽  
Therapeutic Option ◽  
Oncolytic Viruses ◽  
Host Immune System ◽  
Systemic Delivery ◽  
Safety Issues ◽  
Immune Mediated ◽  
Anti Cancer ◽  
Tumor Selectivity

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.

scholarly journals Mesenchymal stem cells and oncolytic viruses: joining forces against cancer

2021 ◽  
Vol 9 (2) ◽  
pp. e001684
Author(s):  
Rafael Moreno
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Immune System ◽  
Oncolytic Viruses ◽  
Immunogenic Cell Death ◽  
The Past ◽  
Physical Barriers ◽  
Immunogenic Properties ◽  
New Strategies

The development of oncolytic viruses (OVs) has increased significantly in the past 20 years, with many candidates entering clinical trials and three of them receiving approval for some indications. Recently, OVs have also gathered interest as candidates to use in combination with immunotherapies for cancer due to their immunogenic properties, which include immunogenic cell death and the possibility to carry therapeutic transgenes in their genomes. OVs transform non-immunogenic ‘cold’ tumors into inflamed immunogenic ‘hot’ tumors, where immunotherapies show the highest efficacy. However, in monotherapy or in combination with immunotherapy, OVs face numerous challenges that limit their successful application, in particular upon systemic administration, such as liver sequestration, neutralizing interactions in blood, physical barriers to infection, and fast clearance by the immune system. In this regard, the use of mesenchymal stem cells (MSCs) as cells carrier for OV delivery addresses many of these obstacles acting as virus carriers and factories, expressing additional transgenes, and modulating the immune system. Here, I review the current progress of OVs-loaded MSCs in cancer, focusing on their interaction with the immune system, and discuss new strategies to improve their therapeutic efficacy.

Recent progress in the battle between oncolytic viruses and tumours

2005 ◽  
Vol 5 (12) ◽  
pp. 965-976 ◽  
Author(s):  
Kelley A. Parato ◽  
Donna Senger ◽  
Peter A. J. Forsyth ◽  
John C. Bell
Keyword(s):  
Recent Progress ◽  
Oncolytic Viruses

scholarly journals Unleashing the Full Potential of Oncolytic Adenoviruses against Cancer by Applying RNA Interference: The Force Awakens

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 228 ◽  
Author(s):  
Tereza Brachtlova ◽  
Victor van Beusechem
Keyword(s):  
Rna Interference ◽  
Immune Responses ◽  
Oncolytic Viruses ◽  
Full Potential ◽  
Anticancer Efficacy ◽  
Host Interactions ◽  
Oncolytic Adenoviruses ◽  
Cellular Factors ◽  
Immunotherapy Of Cancer ◽  
Cellular Pathways

Oncolytic virus therapy of cancer is an actively pursued field of research. Viruses that were once considered as pathogens threatening the wellbeing of humans and animals alike are with every passing decade more prominently regarded as vehicles for genetic and oncolytic therapies. Oncolytic viruses kill cancer cells, sparing healthy tissues, and provoke an anticancer immune response. Among these viruses, recombinant adenoviruses are particularly attractive agents for oncolytic immunotherapy of cancer. Different approaches are currently examined to maximize their therapeutic effect. Here, knowledge of virus–host interactions may lead the way. In this regard, viral and host microRNAs are of particular interest. In addition, cellular factors inhibiting viral replication or dampening immune responses are being discovered. Therefore, applying RNA interference is an attractive approach to strengthen the anticancer efficacy of oncolytic viruses gaining attention in recent years. RNA interference can be used to fortify the virus’ cancer cell-killing and immune-stimulating properties and to suppress cellular pathways to cripple the tumor. In this review, we discuss different ways of how RNA interference may be utilized to increase the efficacy of oncolytic adenoviruses, to reveal their full potential.

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
Keyword(s):  
Oncolytic Viruses ◽  
Anti Cancer

Bioinspired Total Synthesis of Marine Anti-Cancer Meroterpenoids Dysideanone B and Dysiherbol A and Structure Revision of Dysiherbol A

Synlett ◽  
2021 ◽  
Author(s):  
Zhaoyong Lu ◽  
Chuanke Chong
Keyword(s):  
Total Synthesis ◽  
Heck Reaction ◽  
Recent Progress ◽  
Benzyl Bromide ◽  
Radical Cyclization ◽  
Ethoxy Group ◽  
Anti Cancer ◽  
Structure Revision ◽  
A Site ◽  
Intramolecular Heck Reaction

Our recent progress on the total synthesis of marine anti-cancer sesquiterpene quinone/hydroquinone dysideanone B and dysiherbol A was briefly highlighted. This success relied on some key transformations. The union of the terpene and quinone/hydroquinone moieties was realized through a site and stereoselective α-position alkylation of Wieland–Miescher ketone derivative with a bulky benzyl bromide. The 6/6/6/6-tetracycle of dysideanone B was constructed using an intramolecular radical cyclization and the 6/6/5/6-fused core structure of dysiherbol A was forged by an intramolecular Heck reaction, respectively. The possible origin of ethoxy group in dysideanone B was revealed by mimicking the isolation conditions at a late-stage. The structure of dysiherbol A was revised through the total synthesis of this natural product. Schmalz’s synthesis of dysiherbol A was also included.

scholarly journals Do checkpoint inhibitors compromise the cancer patients’ immunity and increase the vulnerability to COVID-19 infection?

Immunotherapy ◽  
2020 ◽  
Author(s):  
Joseph Kattan ◽  
Clarisse Kattan ◽  
Tarek Assi
Keyword(s):  
Cancer Therapy ◽  
Severe Acute Respiratory Syndrome ◽  
Cancer Patients ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Survival Outcomes ◽  
Toxicity Profile ◽  
Anti Cancer ◽  
Acquired Immunodeficiency ◽  
Improvement In Survival

The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has been declared a pandemic by the WHO that claimed the lives of thousands of people within a few months. Cancer patients represent a vulnerable population due to the acquired immunodeficiency associated with anti-cancer therapy. Immune checkpoint inhibitors have largely impacted the prognosis of a multitude of malignancies with significant improvement in survival outcomes and a different, tolerable toxicity profile. In this paper, we assess the safety of ICI administration in cancer patients during the coronavirus pandemic in order to guide the usage of these highly efficacious agents.

scholarly journals Past, Present and Future of Oncolytic Reovirus

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3219
Author(s):  
Louise Müller ◽  
Robert Berkeley ◽  
Tyler Barr ◽  
Elizabeth Ilett ◽  
Fiona Errington-Mais
Keyword(s):  
Immune Responses ◽  
Therapeutic Agent ◽  
Tumour Microenvironment ◽  
Oncolytic Viruses ◽  
Full Potential ◽  
Cellular Mechanisms ◽  
Tumour Immunity ◽  
Combination Strategies ◽  
Significant Attention ◽  
Promising Therapeutic Agent

Oncolytic virotherapy (OVT) has received significant attention in recent years, especially since the approval of talimogene Laherparepvec (T-VEC) in 2015 by the Food and Drug administration (FDA). Mechanistic studies of oncolytic viruses (OVs) have revealed that most, if not all, OVs induce direct oncolysis and stimulate innate and adaptive anti-tumour immunity. With the advancement of tumour modelling, allowing characterisation of the effects of tumour microenvironment (TME) components and identification of the cellular mechanisms required for cell death (both direct oncolysis and anti-tumour immune responses), it is clear that a “one size fits all” approach is not applicable to all OVs, or indeed the same OV across different tumour types and disease locations. This article will provide an unbiased review of oncolytic reovirus (clinically formulated as pelareorep), including the molecular and cellular requirements for reovirus oncolysis and anti-tumour immunity, reports of pre-clinical efficacy and its overall clinical trajectory. Moreover, as it is now abundantly clear that the true potential of all OVs, including reovirus, will only be reached upon the development of synergistic combination strategies, reovirus combination therapeutics will be discussed, including the limitations and challenges that remain to harness the full potential of this promising therapeutic agent.

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