Kate Amato Foundation Awarded Projects
Transcriptomic and epigenetic reprogramming of CAR T cells using the MOTOR platform: an unbiased forward genomics approach
Project Goal: Our lab has developed a chimeric antigen receptor (CAR) that when added to T cells directs them to recognize and kill several types of pediatric cancer cells.
Institution: Baylor College of Medicine
Researchers: Azlann Arnett
Year Awarded: 2024
Type of Childhood Cancer: Embryonal Tumors
Project Description:
Our lab has developed a chimeric antigen receptor (CAR) that when added to T cells directs them to recognize and kill several types of pediatric cancer cells that have a molecule called glypican-3 on their surface including 85% of hepatoblastomas, 75% of Wilms tumors, 85% of hepatocellular carcinomas, up to 100% of malignant rhabdoid tumors, 100% of yolk sac tumors, and approximately 40% of alveolar rhabdomyosarcomas. While this treatment had been proven safe in our ongoing – clinical trials, additional improvements are needed to cure patients because the CAR-T cells eventually become dysfunctional and can no longer effectively kill tumor cells. I developed a system called MOTOR (Model to Optimize Temporal ORFeome Responses) to identify factors that prevent the T cells from becoming dysfunctional or reverse the process that leads to dysfunction. The goal of this proposal is to see if we can identify such factors that improve the function of T cells and determine how they do so. Ultimately, we plan to combine these factors with our CAR to design an improved therapy for pediatric cancer patients.
