Back to results
US 12,622,973 B2Granted
Rejuvenation of CAR T cell
AssigneePurdue Research Foundation
InventorsPhilip Stewart Low, Boning Zhang, John V. Napoleon
Life of this patent
Estimating the term…
Abstract
A payload of drug conjugated to a targeting ligand specifically designed to deliver to exhausted CAR T cells to rejuvenate these CAR T cells is provided herein. The targeted CAR T cells are modified with a fusion receptor which can bind to the targeting ligand and internalize the conjugated payload of drug to execute its regulatory function to exhausted CAR T cell.
Claims18
A system to rejuvenate an exhausted classical CAR T cell comprising at least two components:
- a first component that is a conjugate comprising a targeting ligand covalently linked to a payload drug;
- and
- a second component that is a targeting ligand binding module linked to a membrane-anchoring module,
- wherein:
- the payload drug is a Toll Like Receptor 7 (TLR7) agonist,
- the targeting ligand and the targeting ligand binding molecule are fluorescein isothiocyanate (FITC) and an anti-FITC antibody or fragment thereof, respectively;
- or tacrolimus (FK506) and FK506-binding protein (FKBP), respectively,
- the membrane-anchoring module is a folate receptor,
- the targeting ligand binding module of the second component recognizes the targeting ligand in the first component with high affinity to form a complex,
- the payload drug re-activates the CAR T cell through an antigen-independent pathway, and
- the membrane-anchoring module mediates internalization of the at least two components complex into the exhausted classical CAR T cell.
8 more elements
A method to rejuvenate an exhausted CAR T cell, comprising:
- a. providing to the exhausted CAR T cell a first component comprising a conjugate comprising, a targeting ligand covalently linked to a payload of drug through a releasable linker or a non-releasable linker;
- b. providing said exhausted CAR T cell a second component comprising a fusion receptor, wherein the fusion receptor comprises a targeting ligand binding module linked to a membrane-anchoring module;
- c. wherein the targeting ligand binding module of the second component binds to the targeting ligand in the first component to form a complex,
- d. the membrane-bound receptor module mediates internalization of the complex into the exhausted CAR T cell;
- and
- e. the payload drug re-activates the CAR T cell through an antigen-independent pathway;
- wherein:
- the payload drug is a Toll Like Receptor 7 (TLR7) agonist,
- the targeting ligand and the targeting ligand binding molecule are fluorescein isothiocyanate (FITC) and an anti-FITC antibody or fragment thereof, respectively, or tacrolimus (FK506) and FK506-binding protein (FKBP), respectively, and
- the membrane-anchoring module is a folate receptor.
7 more elements
Dependencies are inferred from the claim text.