Recent advances in oncolytic adenovirus therapies for cancer

Shaw, Amanda Rosewell; Suzuki, Masataka

doi:10.1016/j.coviro.2016.06.009

Cited by 80 publications

(61 citation statements)

References 43 publications

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“…In the tumor microenvironment, accumulation of cancer‐associated fibroblasts and dense extracellular matrix and formation of neovasculature impede the spread of oncolytic adenoviruses throughout the entire tumor mass. To enhance viral dissemination, viruses have been generated to target the extracellular matrix (ECM) . Oncolytic adenoviruses expressing relaxin have been shown to disrupt the ECM and successfully increase viral spreading in tumors .…”

Section: Oncolytic Adenovirus Vectorsmentioning

confidence: 99%

Recent advances in genetic modification of adenovirus vectors for cancer treatment

Yamamoto¹,

Nagasato²,

Yoshida

et al. 2017

Cancer Science

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Adenoviruses are widely used to deliver genes to a variety of cell types and have been used in a number of clinical trials for gene therapy and oncolytic virotherapy. However, several concerns must be addressed for the clinical use of adenovirus vectors. Selective delivery of a therapeutic gene by adenovirus vectors to target cancer is precluded by the widespread distribution of the primary cellular receptors. The systemic administration of adenoviruses results in hepatic tropism independent of the primary receptors. Adenoviruses induce strong innate and acquired immunity in vivo. Furthermore, several modifications to these vectors are necessary to enhance their oncolytic activity and ensure patient safety. As such, the adenovirus genome has been engineered to overcome these problems. The first part of the present review outlines recent progress in the genetic modification of adenovirus vectors for cancer treatment. In addition, several groups have recently developed cancer‐targeting adenovirus vectors by using libraries that display random peptides on a fiber knob. Pancreatic cancer‐targeting sequences have been isolated, and these oncolytic vectors have been shown by our group to be associated with a higher gene transduction efficiency and more potent oncolytic activity in cell lines, murine models, and surgical specimens of pancreatic cancer. In the second part of this review, we explain that combining cancer‐targeting strategies can be a promising approach to increase the clinical usefulness of oncolytic adenovirus vectors.

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Section: Oncolytic Adenovirus Vectorsmentioning

confidence: 99%

Recent advances in genetic modification of adenovirus vectors for cancer treatment

Yamamoto¹,

Nagasato²,

Yoshida

et al. 2017

Cancer Science

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“…Systemic delivery of OAd therapy can cause liver damage and toxicity, especially with Ad5 serotypes, as hexon binding of blood coagulation factor X can result in liver sequestration [62,63]. Therefore, assessing the safety of OAd therapies and potential liver toxicities due to the inherent hepatotropism is essential prior to clinical translation.…”

Section: D Organotypic Modelsmentioning

confidence: 99%

Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives

McKenna

Shaw

Suzuki

2020

Cancers

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Oncolytic adenoviruses (OAd) selectively target and lyse tumor cells and enhance antitumor immune responses. OAds have been used as promising cancer gene therapies for many years and there are a multitude of encouraging pre-clinical studies. However, translating OAd therapies to the clinic has had limited success, in part due to the lack of realistic pre-clinical models to rigorously test the efficacy of OAds. Solid tumors have a heterogenous and hostile microenvironment that provides many barriers to OAd treatment, including structural and immunosuppressive components that cannot be modeled in two-dimensional tissue culture. To replicate these characteristics and bridge the gap between pre-clinical and clinical success, studies must test OAd therapy in three-dimensional culture and animal models. This review focuses on current methods to test OAd efficacy in vitro and in vivo and the development of new model systems to test both oncolysis and immune stimulatory components of oncolytic adenovirotherapy. Author Contributions: Conceptualization, M.S.; Writing-Original Draft, M.K.M.; Writing-Review and Editing, M.K.M., A.R.-S. and M.S.; Supervision, M.S.; Funding Acquisition, M.S. All authors have read and agreed to the published version of the manuscript.

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“…The CRAds are replication-competent adenoviruses that selectively replicate in tumor cells. The restriction of CRAd replication to tumor cells is generally based on a tumor-specific promoter controlling the expression of an essential early adenovirus gene or involves mutations in viral genes,44, 45, 58, 59 allowing CRAds to replicate in tumor cells, but not in normal cells 60 . Su et al 57 .…”

Section: Main Textmentioning

confidence: 99%

Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

Bressy

Hastie

Grdzelishvili

2017

Molecular Therapy - Oncolytics

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Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

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Recent advances in oncolytic adenovirus therapies for cancer

Cited by 80 publications

References 43 publications

Recent advances in genetic modification of adenovirus vectors for cancer treatment

Recent advances in genetic modification of adenovirus vectors for cancer treatment

Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives

Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

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