An oncolytic virus, Ad-TD-nsIL12, has shown promising results in a Phase I clinical trial for patients with recurrent glioblastoma. The study, conducted by researchers from Queen Mary University of London, the Chinese Academy of Sciences, and Capital Medical University in Beijing, demonstrated that the virus treatment was safe and effective at specific doses, leading to complete remission in one patient.
The Phase I, dose-escalation study, published in Nature Communications, involved eight patients with glioblastoma that had recurred after surgery. Patients received one of three dosages of Ad-TD-nsIL12. The research team identified a maximum-tolerated dose, below which the treatment was safe and well-tolerated, with only mild to moderate side effects. Notably, one patient experienced a complete response, with the tumor disappearing entirely, and another showed a partial response, with tumor shrinkage.
Novel Virus Design
The Ad-TD-nsIL12 virus is engineered to deliver a modified version of IL-12, a potent immune-boosting protein. The virus is based on an adenovirus, modified to express a non-secreting form of IL-12 (nsIL12). Normal IL-12 can be extremely toxic in its natural form, but the modified version restricts its release from cells, limiting it to the area surrounding the tumor and preventing systemic toxicity.
Professor Yaohe Wang, co-lead author of the study and inventor of the virus, explained, "Most existing oncolytic viruses are ineffective at low doses and too toxic at higher doses. The key challenge is how to increase efficacy without causing harmful side effects. We believe our approach offers a way forward."
Glioblastoma Context
Glioblastoma is the most common and aggressive type of brain cancer, with a median survival of fewer than 14 months after diagnosis. Current treatments have limited success, and tumor recurrence is common. Oncolytic viruses represent a promising therapeutic strategy, selectively targeting and killing cancer cells while sparing healthy tissue.
Potential for Combination Therapy
The researchers suggest that Ad-TD-nsIL12 could be a promising candidate for combination therapies, potentially working alongside other treatments like immunotherapy. "It's like Yin and Yang," said Professor Wang. "This virus enhances the positive signals that encourage the immune system to attack the tumour, but it could also be paired with treatments that block the tumour's ability to suppress the immune system."
Next Steps
Following these initial results, the team plans to proceed with Phase II trials, led by Professor Hongwei Zhang at Beijing Sanbo Hospital, to further evaluate the treatment's effectiveness in a larger cohort of glioblastoma patients. The researchers also believe that this treatment may hold promise for other cancer types.
The study highlights the importance of international collaboration in advancing cancer research. Professor Wang emphasized, "This collaboration was key to the success of the project, and we look forward to continuing our work together as we develop this promising therapy further."
