Chimeric antigen receptor-targeting monoclonal antibodies
AssigneeBoard of Regents, The University of Texas System
InventorsLaurence JN COOPER, Bipulendu JENA, Harjeet SINGH, David RUSHWORTH
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Abstract
Provided are monoclonal antibodies that detect CD 19 CAR-modified immune cells and CAR-modified immune cells irrespective of the tumor associated antigen they target. Methods of using these functional monoclonal antibodies include, but are not limited to, detection, quantification, activation, and selective propagation of CAR-modified immune cells.
Claims109
An isolated monoclonal antibody, wherein the antibody specifically binds to a chimeric antigen receptor (CAR) polypeptide and wherein the antibody competes for binding of the polypeptide with the 2D3 monoclonal antibody.
A recombinant polypeptide comprising an antibody VH domain comprising CDRs 1-3 of the VH domain of 2D3 (SEQ ID NOs:
- 10, 11 and 12).
A recombinant polypeptide comprising an antibody VL domain comprising CDRs 1-3 of the VL domain of 2D3 (SEQ ID NOs:
- 14, 15 and 16).
A host cell comprising one or more polynucleotide molecule(s) encoding an antibody that binds to the constant domain of a chimeric antigen receptor (CAR) polypeptide.
A method for selecting a cell comprising a chimeric antigen receptor (CAR) polypeptide comprising:
- (a) contacting the cell with an antibody that binds to the constant domain of a chimeric antigen receptor (CAR) polypeptide;
- and
- (b) selecting a cell comprising the CAR based on binding of the antibody.
A cell culture system comprising mammalian T-cells expressing a CAR and an antibody that binds to the constant domain of a CAR polypeptide.
A recombinant cell comprising an expression cassette comprising the coding sequence for an antibody that binds to the constant domain of a CAR polypeptide.
An isolated monoclonal antibody, wherein the antibody specifically binds to a CD19-specific scFv chimeric antigen receptor (CAR) polypeptide and wherein the antibody competes for binding of the polypeptide with the 136.20.1 monoclonal antibody.
A recombinant polypeptide comprising an antibody VH domain comprising CDRs 1-3 of the VH domain of 136.20.1 (SEQ ID NOs:
- 2, 3 and 4).
A recombinant polypeptide comprising an antibody VL domain comprising CDRs 1-3 of the VL domain of 136.20.1 (SEQ ID NOs:
- 6, 7 and 8).
A host cell comprising one or more polynucleotide molecule(s) encoding an antibody that specifically binds to the antigen recognition domain of a Chimeric Antigen Receptor (CAR) polypeptide.
A method for selecting a cell comprising a specific chimeric antigen receptor (CAR) polypeptide comprising:
- (a) contacting the cell with an antibody that specifically binds to the antigen recognition domain of a CAR polypeptide;
- and
- (b) selecting a cell comprising the specific CAR polypeptide based on binding of the antibody.
A cell culture system comprising mammalian T-cells expressing a specific CAR polypeptide and an antibody that specifically binds to the antigen recognition domain of the CAR polypeptide.
A recombinant cell comprising an expression cassette comprising the coding sequence for an antibody that specifically binds to the antigen recognition domain of a CAR polypeptide.
Dependencies are inferred from the claim text.