Synthetic, modular polypeptide system for targeted cell therapy strategies

This technology is a fully synthetic, modular cell receptor system that can be used to facilitate the development of cell-based therapies.

Unmet Need: Ability to efficiently modulate endogenous cellular processes for cell therapy strategies

Current cell-based therapies, including chimeric antigen receptor (CAR) T cells, often require modulation of the endogenous cellular systems and responses for therapeutic applications. Adaptation of cellular systems, which have been refined through the evolutionary process, often requires extensive engineering approaches that can be both time-consuming and costly, limiting the application of cell-based therapies. The ability to efficiently adapt and modulate different cellular processes for therapeutic applications using the same system would enhance the application of cell-based therapies; however, there are currently no systems capable of doing so.

The Technology: Chimeric polypeptide system capable of modulating endogenous cellular processes in multiple cell types

This technology adapts the notch signaling pathway, a well characterized and highly conserved signaling pathway, to modulate cellular processes. This technology is a chimeric polypeptide system consisting of four modular components: an extracellular domain, a force sensor domain, a cleavable transmembrane domain, and intracellular signaling domain. The design of the system allows for the modulation of multiple cellular functions in different cell types, depending on the polypeptide composition. As such, this technology could serve as a platform for cell communication research and can facilitate the development of improved cell-based therapies.

This technology has been validated in Drosophila and multiple cell lines, including T and epithelial cells.

Applications:

• Development of cell-based therapies
• Research tool to monitor cell-signaling pathways
• Development of cell-reporter systems

Advantages:

• Adaptable to multiple signaling pathways and cell types
• Modular design allows for tuning of response based on physiological needs
• System adapted from a well-characterized and highly conserved cell-signaling pathway

Lead Inventor:

Gary Struhl, Ph.D.

Patent Information:

Patent Status

Related Publications:

• Langridge PD, Struhl G. “Epsin-dependent ligand endocytosis activates notch by force” Cell. 2017 Nov 30; 171(6): 1383-1396.

• Roybal KT, Williams JZ, Morsut L, Rupp LJ, Kolinko I, Choe JH, Walker WJ, McNally KA, Lim WA. “Engineering T cells using customized therapeutic response programs using synthetic notch receptors” Cell. 2016 Oct 6; 167(2): 419-432.

• Morsut L, Roybal KT, Xiong X, Gordley RM, Coyle SM, Thomson M, Lim WA. “Engineered customized cell sensing and response behaviors using synthetic notch receptors” Cell. 2016 Feb 11; 164(4): 780-791.

Tech Ventures Reference:

• IR CU18022

• Licensing Contact: [Jerry Kokoshka] (mailto:techtransfer@columbia.edu)