MRI brain scans of one of the trial participants who achieved a complete response. See original paper for more details. © Ning, W. et al. 2024 CC-BY 4.0
Researchers from Queen Mary University of London, the Chinese Academy of Sciences and Capital Medical University in Beijing tested a virus treatment in eight patients with glioblastoma. The treatment was safe and effective below a maximum dose, with complete remission achieved in one patient, supporting progression to phase II clinical trials.
Glioblastoma is the most common and fatal type of brain cancer, with most patients surviving fewer than 14 months after diagnosis. Existing treatments have limited success, and tumour recurrence is common.
Oncolytic viruses – viruses that selectively target and kill cancer cells while leaving healthy cells unharmed – have gained attention as promising treatments and have been tested widely in glioblastoma. However, delivering these treatments is challenging.
"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," said Professor Yaohe Wang, co-lead author of the study and inventor of the virus being tested. "We believe our approach offers a way forward."
In this phase I, dose-escalation study, the team enrolled eight patients with glioblastoma that had returned after surgery. Patients received one of three dosages of the new virus, named Ad-TD-nsIL12. The team identified a maximum-tolerated dose, below which the treatment was safe and well-tolerated, with only mild to moderate side effects. Encouragingly, one patient achieved a complete response, meaning that the tumour disappeared entirely, and another experienced a partial response, with tumour shrinkage.
Professor Wang was able to meet some of the patients his invention has been benefitting in a recent visit to Beijing. "I was introduced to the patient who had a complete response to the treatment, who shook my hand and thanked me," Professor Wang recalls. "I was extremely touched by the experience, and it reinforced the potential of this therapy and the necessity to continue working hard on its development."
The success of the Ad-TD-nsIL12 virus lies in its unique design. The team genetically engineered an adenovirus (a type of virus typically associated with common colds) to deliver a modified version of IL-12 – one of the most potent immune-boosting proteins. IL-12 has shown enormous potential in inhibiting tumour growth but can be extremely toxic in its natural form. To overcome this, the team engineered a version that restricts its release from cells, limiting it to the area surrounding the tumour and preventing it from building up to high levels throughout the body.
The researchers believe 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," explained 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."
Following these early results, the team plans to progress to Phase II trials, which will be led by Professor Hongwei Zhang in Beijing Sanbo Hospital, where this treatment's effectiveness can be more fully assessed in a larger group of patients with glioblastoma. In addition, the researchers believe that this treatment could hold promise in other cancer types.
This work, which brings together experts from Beijing and London, highlights the importance of international collaboration in advancing cancer research. Professor Wang emphasised: "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."
