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Updated: Sep 27, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Efficacy and safety of GC001: an oncolytic vaccinia virus expressing STRIP1 shRNA
Gongchu Li1,2, Gaohui Jiang3, Wei Pang3
1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China. lgc@zstu.edu.cn.
Background:
GC001, a thymidine kinase deleted oncolytic vaccinia virus expressing striatin-interacting protein 1 (STRIP1) shRNA, has been approved by National Medical Products Administration (NMPA) of China to enter phase I clinical trial in 2023.
Methods:
Anti-tumour efficacy of GC001 across multiple cancer types was evaluated in mouse xenograft models. Anti-tumour immune responses were investigated in immunocompetent or humanised cancer mouse model. The mechanism of GC001 activity was elucidated including ROS accumulation, NRF2 degradation, and mitochondrial metabolic reprogramming.
Results:
GC001 showed potent and broad-spectrum anti-tumour activity across multiple mouse xenograft models, and stimulated anti-tumour immune responses in both immunocompetent and humanised mouse models. Importantly, GC001 did not elicit significant toxicity and was well tolerated in the nonhuman primate model. Mechanistically, GC001 induced ROS accumulation, which was driven by NRF2 degradation and mitochondrial metabolic reprogramming through the combinatorial activity of STRIP1 knockdown and oncolytic vaccinia virus backbone, whereas STRIP1 knockdown alone did not induce ROS accumulation.
Conclusions:
Our study reveals dual mechanisms of GC001: viral replication and cytotoxicity potentiation through ROS-Hippo pathway, and oxidative stress-mediated anti-tumour immune responses. Studies have demonstrated robust anti-tumour efficacy and favourable safety profile of GC001, thereby establishing it as a promising oncolytic VV candidate for clinical development.
