Cancer-killing virus offers hope for aggressive brain tumors

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Researchers from Queen Mary University of London, the Chinese Academy of Sciences and Capital Medical University in Beijing tested a viral treatment in eight patients with glioblastoma. The treatment was safe and effective below a maximum dose. Complete remission was achieved in one patient, supporting progression to phase II clinical trials.

Glioblastoma is the most common and deadliest type of brain tumor, with most patients surviving less than 14 months after diagnosis. Existing treatments have limited success and tumor 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 extensively tested in glioblastoma. However, implementing these treatments is challenging.

“Most existing oncolytic viruses are ineffective at low doses and too toxic at higher doses. The biggest challenge is to increase effectiveness without causing harmful side effects,” said Professor Yaohe Wang, co-lead author of the study and inventor of the virus tested. “We believe our approach provides a path forward.”

In this phase I dose-escalation study, the team enrolled eight patients with glioblastomas that had recurred after surgery. Patients received one of three doses of the new virus called 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 the tumor completely disappeared, and another patient achieved a partial response, meaning the tumor shrank.

Professor Wang was able to meet some of the patients who have benefited from his invention during a recent visit to Beijing. “I was introduced to the patient who had a complete response to treatment, who shook my hand and thanked me,” recalls Professor Wang. “This experience touched me deeply and reinforced the potential of this therapy and the need to continue working hard to develop it.”

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 the common cold) to deliver a modified version of IL-12 – one of the most potent immune-boosting proteins. IL-12 has shown tremendous potential for inhibiting tumor growth, but can be extremely toxic in its natural form. To solve this problem, the team developed a version that restricts release from cells, confining it to the area around the tumor and preventing it from accumulating in large quantities throughout the body.

The researchers believe that Ad-TD-nsIL12 could be a promising candidate for combination therapies, potentially working alongside other treatments such as immunotherapy. “It’s like yin and yang,” Professor Wang explained. “This virus enhances the positive signals that encourage the immune system to attack the tumor, but it could also be combined with treatments that block the tumor's ability to suppress the immune system.”

Following these initial results, the team plans to move on to Phase II trials led by Professor Hongwei Zhang at Beijing Sanbo Hospital, where the effectiveness of this treatment can be more fully assessed in a larger group of patients with glioblastoma. Additionally, researchers believe this treatment could hold promise for other types of cancer.

This work, involving experts from Beijing and London, underscores the importance of international collaboration for the advancement of cancer research. Professor Wang emphasized: “This collaboration was key to the success of the project and we look forward to continuing our work together in the further development of this promising therapy.”

Reference: Ning W, Qian X, Dunmall LC, et al. Non-secreting IL12 expressing the oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade gliomas: a phase I study. Nat Commun. 2024;15(1):9299. doi: 10.1038/s41467-024-53041-7

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