Khaled Barakat | University of Alberta
In Vitro Evaluation of DGKa Inhibition to Enhance Immune Responses in Renal Cell Carcinoma
Lay Abstract
Kidney cancer can be tricky to treat. Our bodies have an immune system, which helps us fight off things like infections and even cancer. Special immune cells called NK cells and CD8+ T-cells are like the body’s "soldiers" that attack cancer cells. But in a type of kidney cancer called renal cell carcinoma (RCC), the cancer uses a "sneaky trick" to avoid being attacked by these cells. It makes too much of a protein called DGKa, which stops the immune cells from working properly. When that happens, the NK and CD8+ T-cells can’t kill the cancer cells like they should, and the cancer keeps growing.
How we plan to help. Our research is focusing on a new drug that blocks the DGKa protein. If we can block this protein, it would "wake up" the NK and CD8+ T-cells so they can start killing cancer cells again. This could be a new way to help the immune system fight RCC. On top of that, we believe that combining our new drug with other cancer treatments (like drugs that help the immune system better recognize cancer cells, called immune checkpoint inhibitors) could work even better. This combination might make the immune system even stronger against the cancer.
Why does this research matter? Kidney cancer affects many people every year. Even though there are treatments available, some cancers are hard to treat, especially if they spread to other parts of the body. One reason is that RCC tumors can "hide" from the immune system, so they don’t get attacked like they should. The DGKa protein is a big part of this problem, because it weakens the immune cells that are supposed to fight the cancer. By blocking this protein with our new drug, we hope to stop the cancer from hiding and help the immune system fight back.
What are we doing in our lab? In our lab, we have already made a special drug that blocks the DGKa protein. So far, the drug has worked well in lab tests to block DGKa and help immune cells start working again. Now, we will test this drug on cells from kidney cancer patients to see if it helps the NK and CD8+ T-cells kill cancer cells more effectively. We will also test if combining our drug with immune checkpoint inhibitors makes the immune system even better at attacking the cancer.
We will do experiments to check how well the immune cells work after they’ve been treated with the drug. We expect that by blocking DGKa, the NK and CD8+ T-cells will get better at killing kidney cancer cells. If that happens, the next step would be to test the drug in animals and eventually try it in human clinical trials.
What we hope to achieve. Our big goal is to find a new way to treat kidney cancer, especially for patients whose cancer has been hard to treat with current methods. By blocking DGKa, we want to help the immune system do its job of fighting cancer. If we can make this work, it could mean that people with advanced kidney cancer live longer and have a better quality of life.
Why this research could be a big deal. If our research works, it could be a big step forward in treating kidney cancer. By helping the immune system fight cancer better, we hope to find a new treatment that improves patient outcomes. And since DGKa plays a role in other cancers too, this research might help with more than just kidney cancer in the future.