Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer, with approximately 2400 new cases/year in the United States. Patients are put into remission using chemotherapy, and over 70% stay in remission. If a patient relapses, it is hard to achieve a long-term cure, and they often succumb to their disease. The best chance for maintaining a remission after relapse is often through a stem cell transplant (SCT), in which the patient's bone marrow is replaced with hematopoietic stem cells (HSC) from either a donor or cord blood unit. Part of the reason a cure is achieved using a SCT is that the patient's new immune system can recognize and kill the leukemia cells, a desirable effect that is termed graft versus leukemia (GVL). Not all patients are able to obtain the beneficial GVL effect from SCT, and the aim of this project is to engineer GVL into all cord blood transplants for patients with ALL. This will be done by genetically modifying some of the transferred HSC to encode a receptor that can be expressed on the cell surface and is able to recognize the leukemia cells. The immune cells derived from the modified HSC will then be able to exhibit a GVL effect, with the potential to improve survival.
This project will lay the groundwork for a clinical trial first by developing the methods for generating the genetically modified HSC, and second by testing the modified HSC in a mouse model.