DOTA binding chimeric antigen receptor for cellular therapy
Inventors
Powell, Daniel J. • MINUTOLO, Nicholas • FARWELL, Michael
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12655189-B2
Publication Date
2026-06-16
Expiration Date
Abstract
The present invention includes compositions and methods that utilize a Universal Immune Receptor (UnivIR) CAR system comprising a modified T cell comprising a DOTA CAR and a DOTA-conjugated targeting ligand. In certain embodiments, the invention includes methods for treating, ameliorating, and/or preventing cancer. In certain embodiments, the invention provides a set of complementary molecular imaging tools that is applicable to CAR T cell therapy.
Core Innovation
The invention relates to a modified cell comprising a chimeric antigen receptor (CAR) that includes a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-binding domain, a transmembrane domain, and an intracellular domain. The CAR comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 8, 10, 12, 14, and 16. The disclosed CAR architecture is part of a Universal Immune Receptor (UnivIR) platform using Y-DOTA-related targeting components.
The invention addresses targeted binding and redirected killing using DOTA-based constructs, including reversible versus covalent/irreversible covalent linking via engineered scFv components. The DOTA-binding CAR uses DOTA-conjugated targeting ligands and antibodies to redirect CAR specificity against tumor or disease antigens, rather than relying only on fixed antigen-specific recognition.
The disclosure further links the DOTA-binding CAR framework to companion diagnostic PET imaging and trafficking, as well as to radiolabeled DOTA compounds for PET/SPECT. It also describes imaging-guided modulation of antigen targeting and CAR activity, including adjusting ligand antigen specificity and controlling chelator valency and/or CAR activity in view of toxicity/CRS considerations.
Claims Coverage
The independent claim covers a modified cell having a CAR with a DOTA-binding domain, transmembrane domain, and intracellular domain, where the CAR amino acid sequence is limited to selected SEQ ID NOs. Overall, five inventive features are identified across the provided claim coverage.
Dota-binding CAR architecture
A modified cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises a DOTA-binding domain, a transmembrane domain, and an intracellular domain.
Car amino acid sequence limited to selected SEQ ID NOs
The CAR comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 6, 8, 10, 12, 14, and 16.
Humanized DOTA-binding domain
The DOTA-binding domain is humanized.
CAR defined by nucleic acid sequence selections
The CAR is encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 5, 7, 9, 11, 13, and 15.
Modified cell restricted to immune cell types
The modified cell is selected from a T cell, a macrophage, or an NK cell.
The claims define a modified cell bearing a DOTA-binding CAR with transmembrane and intracellular domains, constrained by specified CAR sequence selections. Dependent claims further narrow the DOTA-binding domain to a humanized form, define alternative nucleic acid SEQ ID NO selections, and limit the modified cell to T cells, macrophages, or NK cells.
Stated Advantages
On-demand, image-guided redirection of CAR cytotoxicity.
Adjusting ligand antigen specificity and modulating chelator valency and/or CAR activity in view of toxicity/CRS considerations.
Non-immunogenicity of the DOTA system.
Tunable regulation using DOTA valency/linker tuning.
Clinical precedent of DOTA-conjugated antibodies.
High valency Her-Bn-DOTA-Y improves tumor reduction versus low valency.
Documented Applications
In vivo cell tracking via PET/CT.
Imaging-guided modulation of antigen targeting and CAR activity.
Radiolabeled DOTA compounds for PET/SPECT.
Activation of DOTA BBz/Dz T cells with Tris-DOTA compounds, assessed by CD69/CD25 (flow cytometry) and IFNγ (ELISA).
In vivo tumor reduction in NSG mice using Her-Bn-DOTA-Y versus low valency constructs, with tumor burden assessed using Skov3 fLuc and bioluminescence imaging.
Interested in licensing this patent?