Ineffective targeting of current CAR T Chimeric antigen receptor (CAR) T cell therapy is a powerful treatment tool for multiple types of malignancies. There are six FDA approved CAR T therapies that have demonstrated efficacy in patients who are refractory to standard chemotherapy, with many patients entering remission after treatment. However, most of these patients relapse within a few months. Relapse has been associated with ineffective targeting of low antigen-expressing malignant cells and/or the inability of CAR T cells to persist for a long period of time after infusion.
CAR Intracellular Domain Constructs A team led by Dr. M. Eric Kohler has designed novel bicistronic CAR constructs that include a LAT (ALAT-CART) or CD3e (CD3e-CART) domain to improve persistence and sensitivity to tumors with low antigen expression and clinically active 2nd Generation CAR T cells. Using CD22 AND CD19 targeting ALAT-CART or CD3e-CART to treat CD22-low acute lymphoid leukemia (ALL) in xenograft mouse models resulted in improved efficacy relative to clinically active 2nd generation CD22 CAR T-cells. Figure 1: Tumor progression in CD22-low ALL mouse models with ALAT-CART (left) and CD3e-CART (right) Furthermore, ALAT-CART and CD3e-CART displayed improved persistence over clinically active 2nd generation CAR T-cell therapies in their CD22-low ALL in-vivo model.
Download Summary Document Here:
https://cuamc.technologypublisher.com/files/sites/cu5685h_and_cu5694h_alat_cart_and_cd3e_cart_ncs_2023.pdf