Targeting cathepsin G in acute myeloid leukemia
The University of North Carolina at Chapel Hill
Project Term: July 1, 2021 - June 30, 2024
We developed a chimeric antigen receptor (CAR) targeting an epitope of the myeloid associated antigen cathepsin G that is processed and presented in the contest of the MHC complex in myeloid leukemic cells. T cells expressing the cathepsin G specific CAR (CG1.CAR) recognize HLA-A2+ myeloid target cells expressing cathepsin G. We intend to study efficacy and safety of CG1.CAR-T cells in preclinical models in preparation of a phase I clinical study in patients with relapsed/refractory AML.
The administration of a subset of human immune cells cultured in the laboratory and known as T lymphocytes that have been engineered to express a chimeric molecule that recognizes leukemic cells (CD19-specific CAR-T cells) has shown remarkable antitumor effects in patients with a blood tumor known as acute lymphoblastic leukemia (ALL). We propose here to develop a similar strategy to treat another form of leukemia known as acute myeloid leukemia (AML) that remains a form of leukemia with few curative options. Developing this type of strategy for AML is challenging because T cells cultured in the laboratory and modified to recognize the tumor cells may not distinguish tumor cells from normal cells. We have developed a strategy that allows the T cells to make this distinction. We thus propose experiments to truly evaluate the efficacy and safety of our proposed strategy before moving the approach to patients with relapsed and refractory AML.