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Oncolytic viruses: overcoming translational challenges
Jordi Martinez-Quintanilla, … , Melissa Chua, Khalid Shah
Jordi Martinez-Quintanilla, … , Melissa Chua, Khalid Shah
Published March 4, 2019
Citation Information: J Clin Invest. 2019;129(4):1407-1418. https://doi.org/10.1172/JCI122287.
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Review

Oncolytic viruses: overcoming translational challenges

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Abstract

Oncolytic virotherapy (OVT) is a promising approach in which WT or engineered viruses selectively replicate and destroy tumor cells while sparing normal ones. 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. These clinical trials have revealed several critical limitations with regard to viral delivery, spread, resistance, and antiviral immunity. Here, we focus on promising research strategies that have been developed to overcome the aforementioned obstacles. Such strategies include engineering OVs to target a broad spectrum of tumor cells while evading the immune system, developing unique delivery mechanisms, combining other immunotherapeutic agents with OVT, and using clinically translatable mouse tumor models to potentially translate OVT more readily into clinical settings.

Authors

Jordi Martinez-Quintanilla, Ivan Seah, Melissa Chua, Khalid Shah

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Figure 1

Strategies to circumvent the obstacles observed in clinical trials using OVs.

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Strategies to circumvent the obstacles observed in clinical trials using...
(A) Enhancing intratumor viral spread. OVs engineered to express hyaluronidase (HD) are able to break down HA in the ECM, enhancing the ease of intratumor spread of the OV. (B) Sensitize tumor cells to OV therapy. OVs engineered to secrete proapoptotic proteins revert tumor resistance to OV therapies. (C) Optimizing OV delivery. Carrier cells protect OVs from the immune system and increase tumor targeting of OVs. (D) OV-mediated immunotherapy. OV-mediated oncolysis boosts the immune system response against tumor cells, improving overall therapeutic response.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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