Andrei Thomas-Tikhonenko, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

Our overarching goal is to develop new therapies for T-cell acute lymphoblastic leukemia (T-ALL). T-ALL is a particularly aggressive pediatric blood cancer. In the past, researchers tried to target T-ALL with immunotherapies known as CAR T-cells, or CARTs. However, these approaches were usually unsuccessful. This is because surface markers used to label cancer cells are also found on CAR T cells themselves. This causes CARTs to commit “fratricide”. Thus, there is an urgent need to find targets that are unique to cancerous T-cells. Our research has identified one such target called P2RX5. P2RX5 is often thought to be inactive in humans because of widespread inherited mutations. However, we determined that the active version of this gene is still common in people of African and, to a lesser extent, Hispanic origins. What makes it particularly attractive is that CARTs don’t make P2RX5, but high-risk T-ALL cells do. Encouraged by these findings, we created an antibody that can latch onto P2RX5-making cells. We then converted this antibody into CARTs, dubbing them “CART-X5”. Early results showed that CART-X5s can kill cancer cells without harming themselves. Our current plan is to test this approach in mice with leukemia. We see this work as a first step towards clinical trials in humans. While CART-X5 could work only in patients of certain ancestries, the very same patients have far less access to immunotherapy. Bringing CART-X5 to the clinic would reduce these disparities.