Novel Costimulatory Platform for CAR-Based Adoptive Cell Therapies


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.


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For Information, Contact:
Doreen Molk
University of Colorado
Mark Kohler
Terry Fry
Catherine Danis
Lillie Leach
Disease Areas:
Regenerative Medicine
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