Background 

Our immune system is designed to protect us from illnesses, including cancer. Some cancer treatments, called immunotherapies, help the immune system find and destroy cancer cells. In bladder cancer, a treatment called BCG has been successful for many patients with early-stage cancer. However, not everyone responds to BCG, and sometimes the cancer comes back or spreads, leaving BCG no longer effective.

This study focused on finding new immunotherapy treatments that can work not only for early-stage bladder cancer but also for more advanced, metastatic cancer. 

What This Research Proposes to Address 

The research team studied a type of treatment called oncolytic viruses. These are special viruses that can attack cancer cells and also help the immune system fight back against tumors. One of these viruses, called Newcastle Disease Virus (NDV), has shown promise.

The researchers found that NDV can activate the immune system to recognize and kill bladder cancer cells. When NDV is used along with other immune-based treatments, it has even helped shrink tumors that had spread. A genetically-engineered version of NDV—made even stronger at activating the immune system—worked even better in fighting cancer in earlier studies. 

Why This Research Is Important 

Cancer tumors often develop ways to hide from the immune system. This makes them harder to treat because they can resist both immunotherapy and virus-based therapies. The goal of this study was to discover exactly how bladder cancer escapes the immune system’s attack. By learning these details, researchers can design smarter treatments that prevent tumors from resisting therapy.

The team also tested different versions of genetically-engineered NDV to see which ones work best at killing bladder cancer. The most promising virus candidates moved forward into future clinical trials, which test treatments in patients. 

Final Report Summary

Immunotherapy is a type of treatment that helps the body’s immune system fight cancer. Some drugs that target proteins called CTLA-4 and PD-1 have already been approved, as well as a new one for advanced bladder cancer. These treatments work well for some patients, but not for everyone. Doctors need better ways to predict who will respond and to find safe treatment combinations. 
 
One idea was to combine these drugs with a different approach that uses a harmless virus called Newcastle Disease Virus (NDV). When NDV is injected directly into a tumor, it can wake up the immune system to attack cancer. In animal studies, NDV alone worked well, but it also triggered breaks in the immune system that limited its power. When NDV was combined with the CTLA-4 or PD-1 drugs, the results were much stronger. Tumors that were injected with the virus, as well as other tumors in the body, were destroyed, and the immune system stayed active against cancer for a long time. 
 
Scientists also found that changing NDV to carry an extra immune-boosting gene made it even more effective. These results are promising, and clinical trials are being planned to test this strategy in bladder cancer patients. 

Zamarin, D., Holmgaard, R. B., Ricca, J., Plitt, T., Palese, P., Sharma, P., Merghoub, T., Wolchok, J. D., & Allison, J. P. (2017). Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity. Nature communications, 8, 14340. https://doi.org/10.1038/ncomms14340

None Reported as of August 2025

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