Engineering new CAR T-cell treatments for pediatric leukemia

“As a physician-scientist, I spend 20% of my time treating patients,” Richards said. “I see the challenges that they face with standard chemotherapy. It provides a lot of motivation for me to come back to the lab and make an impact with my research.”

Richards, a physician-scientist with UW Carbone Cancer Center and Assistant Professor in the Division of Pediatric Hematology, Oncology, and Bone Marrow Transplant, researches and mechanically engineers chimeric antigen receptor (CAR) T-cell therapies that treat pediatric cancers, specifically the blood cancer acute myeloid leukemia (AML).

AML develops when there is a genetic mutation in precursor bone marrow cells that cause unrestricted cancer cell growth, choking the necessary nutrients the body needs to create healthy blood cells. Instead of forming a solid tumor, blood cancers like AML spread throughout the entire body.

CARs are synthetic receptors that can be expressed on a patient’s own T-cells to allow them to target and destroy cancer cells. CAR T-cell therapy has made a tremendous positive impact for patients with high-risk B cell malignancies, but there has not been as much progress for patients with myeloid malignancies.

Richards’s goal is to identify barriers to this progress and to study the challenges in her lab so that CAR T-cell therapies can be used to treat patients with AML.

Unlike chemotherapy, which is meant to kill cancerous cells but can simultaneously harm healthy cells, immunotherapy harnesses a patient’s own immune system to fight their cancer more selectively. Richards’s goal is to treat cancer without increasing toxicity in the human body.

“CAR T-cells are targeted to something specific on the surface of a cancer cell that is not expressed in healthy cells,” Richards said. “They avoid some of the side effects that come with chemotherapy.”

Richards and her team construct these CAR T-cells in her lab. During this 10-day process, she starts with normal T-cells from healthy human blood donors and uses viruses to force these T cells to express cancer-targeting receptors. Richards then runs these synthetic CAR T-cells through various pre-clinical trials to see how well they eliminate cancer and protect the healthy cells. If they do threaten healthy cells, there must be a way to mitigate the harm.

Once these steps have been completed, theoretically, the CAR T-cells can be moved into patients.

“My long-term goal is to develop a therapy in my lab that directly benefits patients,” Richards said.

She is also collaborating with Dr. Joshua Brockman, an assistant professor in the Department of Biomedical Engineering, to perform research on the mechanics of the CAR T-cell proteins. Their work will probe exactly how the CAR T-cells that she creates in the lab transmit signals to their oncolytic targets and what makes the two bind together. Knowing this can help improve treatment effectiveness.

“Every small discovery we’re making has the potential to advance knowledge and build ideas that could lead to clinical improvements,” Richards said.