Background
Bladder cancer is one of the most common cancers of the urinary system. A newer drug called enfortumab vedotin (EV) targets a protein on bladder cancer cells known as Nectin-4. While EV has helped many patients, long-term outcomes are still limited. Because most bladder tumors continue to carry the Nectin-4 protein, this protein remains an important target for developing better treatments.

This project focuses on creating a new type of treatment that uses living immune cells instead of traditional drugs or chemotherapy. The immune cells used are called natural killer (NK) cells. NK cells can naturally find and destroy cancer cells. Unlike some other cell therapies that must be made separately for each patient, NK cell therapies can be prepared in advance from healthy donors and used for many patients. This approach may make treatment faster, more affordable, and more widely available. In bladder cancer, NK cells can be delivered either through the bloodstream or directly into the bladder.

What the Study Proposes to Address
The research team plans to improve how NK cells recognize bladder cancer cells. To do this, they will add a special receptor called a chimeric antigen receptor (CAR). This receptor acts like a molecular GPS that directs NK cells to the Nectin-4 protein on tumor cells. These engineered cells are called Nectin-4 CAR-NK cells.

The study has three main goals. First, the team will build and test Nectin-4 CAR-NK cells in bladder cancer models. Second, they will look for weak points in tumor cells and test whether blocking these weak spots with existing drugs improves how well NK cells kill cancer. Third, they will work to strengthen NK cells using natural signals that may improve their survival and effectiveness.

Why This Research is Important
This research aims to lay the groundwork for a new treatment option for bladder cancer. By improving how NK cells find and attack cancer cells, the study may help support the development of a therapy that is safe, effective, and more accessible to patients.