Intratumoral delivery of a novel oncolytic adenovirus encoding human antibody against PD-1 elicits enhanced antitumor efficacy

Molecular Therapy: Oncolytics

Hongyang Shi¹  Xi Yang²  Yingying Guo²  Xuchen Wang²  Man Xing³  Xiang Wang³  Ping Zhou³  Zhong Huang⁴  Dongming Zhou⁴  Mangteng Wu⁴  Shubing Tang⁴  Caihong Zhu⁴ 

[1] Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;University of Chinese Academy of Sciences, Beijing 100049, China;Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China;Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China;

关键词: chimpanzee adenovirus;    oncolytic virus;    checkpoint inhibitors;    PD-1;    combination cancer therapy;    alternative;   

DOI  :  

来源: DOAJ

【 摘 要 】

To date, diverse combination therapies with immune checkpoint inhibitors (ICIs), particularly oncolytic virotherapy, have demonstrated enhanced therapeutic outcomes in cancer treatment. However, high pre-existing immunity against the widely used adenovirus human serotype 5 (AdHu5) limits its extensive clinical application. In this study, we constructed an innovative oncolytic virus (OV) based on a chimpanzee adenoviral vector with low seropositivity in the human population, named AdC68-spE1A-αPD-1, which endows the parental OV (AdC68-spE1A-ΔE3) with the ability to express full-length anti-human programmed cell death-1 monoclonal antibody (αPD-1). In vitro studies indicated that the AdC68-spE1A-αPD-1 retained parental oncolytic capacity, and αPD-1 was efficiently secreted from the infected tumor cells and bound exclusively to human PD-1 (hPD-1) protein. In vivo, intratumoral treatment with AdC68-spE1A-αPD-1 resulted in significant tumor suppression, prolonged overall survival, and enhanced systemic antitumor memory response in an hPD-1 knockin mouse tumor model. This strategy outperformed the unarmed OV and was comparable with combination therapy with intratumoral injection of AdC68-spE1A-ΔE3 and systemic administration of commercial αPD-1. In summary, AdC68-spE1A-αPD-1 is a cost-effective approach with potential clinical applications. ‬‬‬‬

【 授权许可】

Unknown