Neoantigen-specific T cells for CBFA2T3-GLIS2 driven pediatric acute megakaryoblastic leukemia
Acute megakaryoblastic leukemia (AMKL) carrying the CBFA2T3::GLIS2 mutation is a subtype of pediatric leukemia with a poor prognosis. We propose to investigate the interaction between this leukemia and the immune system, with a particular focus on identifying T cells that recognize and eliminate CBFA2T3::GLIS2 leukemia cells. In preliminary studies we have established a system to identify T cells that recognize the leukemia cells, determine the protein on these T cells responsible for recognition (called a T cell receptor) and then engineered T cells to contain these T cell receptors so that they can be used as a cellular therapy. We will now go on to identify the protein in the leukemia cells that the T cell receptors are recognizing and determine how effective the T cell therapy is in model systems. This research will contribute to the development of novel immunotherapies for AMKL to improve patient outcomes.
Project Goals
The goal of these studies is to (1) determine the effectiveness of our engineered T cells in eliminating CBFA2T3::GLIS2 leukemia cells using model systems and (2) identify the protein(s) in the leukemia cells that the engineered T cells are recognizing. An understanding of the leukemia protein(s) that are being targeted can be used to further refine the engineered T cells to improve upon their activity and/or select T cells that are recognizing proteins required by the leukemia cell to function making immune escape less likely.
