LOCKR-mediated CAR T cell recruitment

A cell and cell therapy technology, applied in the field of LOCKR-mediated CAR T cell recruitment, can solve problems such as difficult to re-use

Pending Publication Date: 2022-05-06
UNIV OF WASHINGTON +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] Biology is good at integrating multiple signals to control function; however, natural systems are highly evolved for specific functions, making ...

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  • LOCKR-mediated CAR T cell recruitment
  • LOCKR-mediated CAR T cell recruitment
  • LOCKR-mediated CAR T cell recruitment

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[0488] overview

[0489] Natural biological systems integrate multiple protein-binding inputs through post-translational signaling cascades that are hard-coded into specialized functions; synthetic systems capable of integrating multiple binding inputs through conformational switching could be a general solution for predictively controlling multiple biological functions . We describe the computational design of proximity-activated de novo protein switches that perform AND, OR, and NOT Boolean logic operations, and combinations thereof, in response to precise combinations of protein-binding events. These switches are activated by a conformational change only if all logical conditions are met, and the high-resolution X-ray crystal structure confirms this design model. We demonstrate the utility of this system for hyperspecific targeting of mammalian cells, which are distinguished in complex cell populations only by their precise combination of surface markers. We implemented t...

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Abstract

The present invention discloses a method for isolating bioactive peptides and/or binding domains in an inactive ("off") state until binding to a second designed polypeptide, referred to as a key, only when a protein switch component is co-localized when bound to its target. The polypeptides induce protein switches that activate ("open") the conformational change of the bioactive peptide or binding domain, components of such protein switches, and uses thereof.

Description

[0001] cross reference [0002] This application claims priority to U.S. Provisional Patent Application Serial No. 62 / 848840, filed May 16, 2019, and U.S. Provisional Patent Application Serial No. 62 / 964024, filed January 21, 2020, which are incorporated by reference The entire contents are incorporated herein. [0003] Federal Funding Statement [0004] This invention was made under Government Grant No. CHE-1629214 awarded by the National Science Foundation, Grant No. HDTRA1-18-1-0001 awarded by the Defense Threat Reduction Agency (DTRA), and Grant No. R01CA114536 awarded by the National Institutes of Health carried out with funding. The government has certain rights in this invention. [0005] Sequence Listing References Submitted Electronically via EFS-WEB [0006] This application contains a sequence listing submitted in the form of an electronic text file named "19-852-PCT_Sequence-Listing_ST25.txt", with a size of 32MB and created on May 14, 2020. Pursuant to 37 CFR §...

Claims

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Application Information

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IPC IPC(8): C12N5/10C07K19/00C12N15/85
CPCC12N5/0636C07K16/28C07K14/7051C12N15/85C12N2510/00C12N2800/107C07K2319/02C07K2319/03C07K2319/33C07K2319/74C12N15/1037A61K35/17A61K39/0011A61K2039/5156C07K2317/622C07K16/32C07K16/2863C07K16/30C07K2318/20A61K38/1774C07K14/005C07K14/4747C07K14/70596C07K2319/30C12N15/625C12N15/86C12N2501/2302C12N2740/15043
Inventor 大卫·贝克斯科特·博伊肯麦克·约瑟夫·拉约伊罗伯特·A·兰甘斯坦利·R·里德尔亚历山大·索尔特
Owner UNIV OF WASHINGTON
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