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Virus-Protein Corona Replacement Strategy to Improve the Antitumor Efficacy of Intravenously Injected Oncolytic
Hanwei Huang1,2,3, Mingyang Liu1,2,3, Mengchi Sun4
1Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University155 North Nanjing Street, 110000, Heping District, Shenyang, China.
Abstract:
Intravenous administration of oncolytic adenoviruses (OVs) is a hopeful tumor therapeutic modality. However, the sharp clearance of OVs by the immune system dampens its effectiveness. Many studies have attempted to extend the circulation of intravenously administered OVs, almost all by preventing OVs from binding to neutralizing antibodies and complements in the blood, but the results have not been satisfactory. In contrast to previous conclusions, we found that the key to improving the circulation of OVs is to prevent the formation of the virus-protein corona rather than simply preventing the binding of neutralizing antibodies or complements to OVs. After identifying the key protein components of the virus-protein corona, we proposed a virus-protein corona replacement strategy, where an artificial virus-protein corona was formed on OVs to completely prevent the interaction of OVs with key virus-protein corona components in the plasma. It was found that this strategy dramatically prolonged the circulation time of OVs by over 30 fold and increased the distribution of OVs in tumors by over 10-fold, resulting in superior antitumor efficacy in primary and metastatic tumor models. Our finding provides a perspective on intravenous delivery of OVs, shifting the focus of future studies from preventing OV binding with neutralization antibodies and complements to preventing OVs from interacting with key virus-protein corona components in the plasma.
Insights
Researchers found that preventing virus-protein corona formation, not just antibody binding, is key to extending oncolytic adenovirus (OV) circulation for better tumor treatment. This strategy significantly improved OV delivery and efficacy.
Area of Science:
- Oncolytic virotherapy
- Nanomedicine
- Immunology
Background:
- Intravenous administration of oncolytic adenoviruses (OVs) shows promise for cancer therapy.
- Rapid clearance by the immune system limits the effectiveness of systemically delivered OVs.
- Previous strategies focused on preventing antibody and complement binding, with limited success.
Purpose of the Study:
- To identify the primary factor limiting the circulation of intravenously administered OVs.
- To develop a novel strategy to enhance OV circulation and tumor targeting.
- To improve the antitumor efficacy of OV therapy.
Main Methods:
- Identified key protein components of the virus-protein corona formed on OVs.
- Developed a virus-protein corona replacement strategy using artificial coronas.
- Evaluated the impact of the strategy on OV circulation time, tumor distribution, and antitumor efficacy in preclinical models.
Main Results:
- Preventing virus-protein corona formation, rather than just antibody/complement binding, is crucial for prolonging OV circulation.
- The virus-protein corona replacement strategy increased OV circulation time over 30-fold.
- OV distribution in tumors increased over 10-fold, leading to superior antitumor effects.
Conclusions:
- The formation of virus-protein corona is a critical barrier to effective intravenous OV delivery.
- A virus-protein corona replacement strategy offers a promising approach to enhance OV circulation and tumor targeting.
- Future research should focus on mitigating virus-protein corona interactions for improved oncolytic virotherapy.
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