Notch Activation to Improve Persistence and Efficacy of T Cell Therapies

Technology Overview

While CAR T-based cell therapies are promising, the persistence, proliferation, and efficacy of those engineered T cell therapies need to be improved. Additionally, less differentiated T cell subsets (Tscm, Tcm) have been shown to deliver better anti-tumor efficacy. Researchers at the Fred Hutchinson Cancer Center have developed a method of using Notch ligands during culturing to improve the persistence and efficacy of CAR T cell therapies. Signaling through NOTCH during culture of naïve T cells resulted in a less differentiated phenotype based on CD45RO, CD62L, and activation markers (PD-1, LAG-3, CD69). Culturing T cells in the presence of NOTCH signals did not inhibit proliferation and functionality, and the CAR T cells show superior efficacy over un-stimulated CAR T cells.

Applications

•         CAR T cell therapy manufacturing
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Advantages

•         Attaching Notch ligands to a culture vessel for CAR T cell generation is a simple addition
• The approach of adding engineered Notch ligand to the culture vessel wall has been utilized in FDA approved clinical trials (for cord blood expansion)
• In vitro characterization has shown enrichment of phenotypically naïve T cells
• In vivo experiments show significant increase in efficacy of CAR T cells targeting CD19

Patent Information

• US Patent Application Filed: 17/272,117

Investigator Overview

• Irwin Bernstein, M.D. - Professor, Translational Science and Therapeutics Division, Fred Hutch