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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Challenges and progress toward tumor-targeted therapy by systemic delivery of polymer-complexed oncolytic
Thavasyappan Thambi1, JinWoo Hong2, A-Rum Yoon1,3
1Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro Seongdong-gu, Seoul, 04763, Korea.
Abstract:
Oncolytic adenovirus (oAd) elicits antitumor activity by preferential viral replication in cancer cells. However, poor systemic administrability or suboptimal intratumoral retainment of the virus remains a major challenge toward maximizing the antitumor activity of oAd in a clinical environment. To surmount these issues, a variety of non-immunogenic polymers has been used to modify the surface of oAds chemically or physically. Complexation of oAd with polymers can effectively evade the host immune response and reduces nonspecific liver sequestration. The tumor-specific delivery of these complexes can be further improved upon by inclusion of tumor-targeting moieties on the surface. Therefore, modification of the Ad surface using polymers is viewed as a potential strategy to enhance the delivery of Ad via systemic administration. This review aims to provide a comprehensive overview of polymer-complexed Ads, their progress, and future challenges in cancer treatment.
Insights
Polymer modification of oncolytic adenoviruses (oAds) improves systemic delivery and tumor retention. This strategy enhances antitumor activity by overcoming challenges in viral administration for cancer treatment.
Area of Science:
- Biomedical Engineering
- Oncology
- Virology
Background:
- Oncolytic adenoviruses (oAds) show promise for cancer treatment via selective replication in tumor cells.
- Clinical application is limited by poor systemic delivery and insufficient intratumoral retention of oAds.
- Current strategies focus on enhancing viral efficacy and safety for broader therapeutic use.
Purpose of the Study:
- To review the advancements in polymer-modified oncolytic adenoviruses (oAds) for cancer therapy.
- To explore how polymer complexation addresses challenges in oAd delivery and efficacy.
- To discuss the future prospects and hurdles in the clinical translation of polymer-complexed oAds.
Main Methods:
- Chemical and physical modification of adenovirus surfaces using non-immunogenic polymers.
- Complexation of oAds with polymers to evade immune responses and reduce liver sequestration.
- Incorporation of tumor-targeting moieties onto polymer-oAd complexes for enhanced tumor specificity.
Main Results:
- Polymer modification improves the systemic administrability of oAds.
- Complexation with polymers enhances viral evasion of host immune surveillance.
- Surface modifications can lead to improved tumor-specific delivery and retention of oAds.
Conclusions:
- Polymer-complexed oAds represent a promising strategy to enhance cancer treatment efficacy.
- Further research is needed to optimize polymer design and targeting moieties for clinical success.
- Overcoming delivery and retention challenges is crucial for maximizing the therapeutic potential of oAds.
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