Childhood cancer research

Dr. Kudek has dedicated his life to researching better treatments for children with neuroblastoma, the most common non-brain solid tumor in children. Currently, patients with high-risk neuroblastoma are treated with radiation, chemotherapy, surgery, stem cell transplants and immunotherapy, but survival rates hover at just 50%. “A lot of accomplishments have been made, but there is room for improvement,” Dr. Kudek said. “My interests lie in finding new immunotherapies and new targeted therapies to treat childhood cancers. Our research uses different elements of the immune system to do just that.”

His current research project is a modification of Dr. Cui’s bladder cancer research, which focuses on studying T cells, a type of immune cell that helps to protect against viral and bacterial infections, but loses its effectiveness against diseases like cancer. Dr. Cui and Dr. Kudek are interested in learning how T cells can be re-energized to fight tumors. “It’s a way of using the blood and its components to get into solid tumors where they can then do their job,” Dr. Kudek said.

This therapy, called CAR-T, has shown some effectiveness in leukemia in lymphoma; however, it has not worked as well in solid tumors because of differences in the immune system and types of malignant cells. In addition to its cancerous cells, tumors contain a number of immune cells that suppress the immune system’s ability to kill harmful cells, essentially making the immune system work against itself. In addition, the tumor consumes blood and nutrients that the immune system needs to function properly.

Dr. Kudek is interested in using modified T cells to recognize markers on tumor cells so that if/when T cells come into contact with tumor cells, they recognize them as foreign, become activated and kill the harmful cells. But tumors are tricky, and often mutate away from certain therapeutic targets, or become independent of them. “The big challenge is getting the T cells into a place where they can recognize that marker on the surface of the tumor,” he said.

Combatting side effects of new treatments

In addition to studying how T cells can be used to treat pediatric neuroblastoma, Dr. Kudek is interested in learning more about the side effects of cellular therapies used to treat cancer. For example, patients with high-risk blood cancer often receive stem cell and bone marrow transplants to replace their faulty immune systems with one that is capable of recognizing and wiping out tumors. However, sometimes, the “new” immune system identifies normal, healthy tissues as threats—something called graft vs. host disease. “I’m interested in learning more about what role the different types of T cells play in graft vs. host disease and how that’s impacted by different changes in the person’s body,” he said. “This will hopefully improve on the responses patients get from bone marrow transplants, while simultaneously learning how to minimize the graft vs. host response.”

Moving the needle

Dr. Kudek believes that Versiti’s collaborative environment, as well as its affiliation with and connection to the Medical College of Wisconsin, puts it in a prime position to make a difference in patients’ lives. “I like the collaboration at Versiti; I like how close everybody’s labs are, not just in proximity, but in a shared vision of what we’re trying to do,” he said. “Versiti is growing a critical mass of researchers and scientists interested in this type of research. The close collaboration with MCW places Versiti in a prime position to help move the needle.”

About the expert: Matthew Kudek, MD, is an assistant investigator at Versiti Blood Research Institute and an assistant professor of pediatric oncology in the Department of Pediatric Hematology, Oncology and Bone Marrow Transplantation at the Medical College of Wisconsin.