Related Experiment Video
Updated: Jun 1, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Hyperacute rejection-engineered oncolytic virus for interventional clinical trial in refractory cancer patients
Liping Zhong1, Lu Gan1, Bing Wang2
1State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Medical University, Nanning, Guangxi 530021, China.
Abstract:
Recently, oncolytic virus (OV) therapy has shown great promise in treating malignancies. However, intravenous safety and inherent lack of immunity are two significant limitations in clinical practice. Herein, we successfully developed a recombinant Newcastle disease virus with porcine α1,3GT gene (NDV-GT) triggering hyperacute rejection. We demonstrated its feasibility in preclinical studies. The intravenous NDV-GT showed superior ability to eradicate tumor cells in our innovative CRISPR-mediated primary hepatocellular carcinoma monkeys. Importantly, the interventional clinical trial treating 20 patients with relapsed/refractory metastatic cancer (Chinese Clinical Trial Registry of WHO, ChiCTR2000031980) showed a high rate (90.00%) of disease control and durable responses, without serious adverse events and clinically functional neutralizing antibodies, further suggesting that immunogenicity is minimal under these conditions and demonstrating the feasibility of NDV-GT for immunovirotherapy. Collectively, our results demonstrate the high safety and efficacy of intravenous NDV-GT, thus providing an innovative technology for OV therapy in oncological therapeutics and beyond.
Insights
A novel oncolytic virus therapy using Newcastle disease virus with porcine α1,3GT gene (NDV-GT) demonstrated high safety and efficacy in preclinical and clinical studies for cancer treatment. This innovative immunovirotherapy shows promise for overcoming limitations in current oncological treatments.
Area of Science:
- Oncology
- Virology
- Immunotherapy
Background:
- Oncolytic virus (OV) therapy shows promise for cancer treatment but faces limitations in intravenous safety and immunogenicity.
- Developing safe and effective OVs is crucial for advancing cancer immunotherapy.
Purpose of the Study:
- To develop and evaluate a recombinant Newcastle disease virus with porcine α1,3GT gene (NDV-GT) for enhanced safety and efficacy in cancer treatment.
- To assess the preclinical and clinical performance of intravenous NDV-GT in eradicating tumors and controlling disease progression.
Main Methods:
- Development of a recombinant Newcastle disease virus (NDV-GT) incorporating the porcine α1,3GT gene.
- Preclinical evaluation in CRISPR-mediated primary hepatocellular carcinoma (PHC) monkeys.
- Interventional clinical trial in patients with relapsed/refractory metastatic cancer.
Main Results:
- Intravenous NDV-GT demonstrated superior tumor cell eradication in preclinical PHC models.
- The clinical trial (ChiCTR2000031980) showed a 90% disease control rate with durable responses in 20 patients.
- No serious adverse events were observed, and minimal clinically functional neutralizing antibodies were detected, indicating low immunogenicity.
Conclusions:
- Intravenous NDV-GT is a safe and effective oncolytic virus therapy for cancer.
- NDV-GT offers an innovative approach to immunovirotherapy, overcoming key limitations of traditional OV therapies.
- This technology holds significant potential for oncological therapeutics and beyond.
