Babak Moghimi, MD

Since the last update, they have built a highly realistic 3D bone-marrow organoid model that mimics the environment where AML grows, allowing them to test how well their engineered CAR T cells kill leukemia while sparing healthy stem cells. Additionally, they created a new mouse model of AML with a fully intact immune system, giving them a more rigorous and clinically relevant way to evaluate safety and effectiveness. In parallel, the team has begun uncovering how a key gene, RUNX3, can be used to fine-tune the activation and durability of their CAR T cells, helping them function longer and resist exhaustion. Together, these advances significantly strengthen the pathway toward a safer, more effective CAR T cell therapy designed to reduce side effects, prevent tumor escape, and improve outcomes for children with AML.

Over the past six months, they have developed sophisticated lab models that allow them to precisely control the expression of leukemia markers on cancer cells. This system mimics how tumors in real patients often try to “escape” detection, giving the team powerful tools to study and prevent this resistance. In addition to this, they have enhanced the internal signaling strength of the CAR T cells by modifying a key protein called ZAP70, helping the cells respond more effectively to cancer while avoiding overstimulation that could lead to dangerous side effects. To further improve safety and durability, they are building finely tuned genetic control systems within the T cells to regulate when and how strongly they respond. The team is also streamlining the CAR design to make it more compact and better suited for delivery using gene therapy technologies. Together, these advances are laying the groundwork for a more precise, safer, and durable CAR T cell therapy that could enter clinical testing and ultimately expand treatment options for children with hard-to-treat AML.

During this reporting period, they focused on optimizing CAR T cell signaling by evaluating specific components of the signaling cascade to enhance activation and improve their effectiveness. The team also developed models that mimic patient conditions by varying levels of CD33 and CD123 antigens, enabling the study of immune escape mechanisms. Finally, they have streamlined the CAR T cell design, creating a more compact and efficient structure that simplifies packaging and enhances the potential for advanced clinical applications. These achievements represent significant progress in CAR T cell optimization and lay a solid foundation for next-generation therapies targeting pediatric AML.