journal article·2023-08-08

Virus-Protein Corona Replacement Strategy to Improve the Antitumor Efficacy of Intravenously Injected Oncolytic Adenovirus

Hanwei Huang, Mingyang Liu, Mengchi Sun, Shijie Duan, Siwei Pan, Pengfei Liu, Zhenguo Cheng, Onder Ergonul, Füsun Can, Zhenning Wang, Zhiqing Pang, Funan Liu

ACS Nano· Volume 17· Issue 15
Publisher page

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.
Source: openalex_inverted_index · Quality: baseline

Research context

OpenAlex topics: Virus-based gene therapy research · CAR-T cell therapy research · RNA Interference and Gene Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University155 North Nanjing Street, 110000, Heping District, Shenyang, China

Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, 200120 Shanghai, China

Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, 155 North Nanjing Street, 110000, Heping District, Shenyang, China

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, P. R. China

Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450052, China

Koç University Iş Bank Center for Infectious Diseases (KUISCID), Koç University School of Medicine and American Hospital, Istanbul 34450, Turkey

Phase I Clinical Trials Center, The First Hospital, China Medical University, 518 North Chuangxin Road, Baita Street, Hunnan District, Shenyang 110102, Liaoning, China

Funding

National Key Research and Development Program of China · Liaoning Revitalization Talents Program · National Natural Science Foundation of China

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