Covalent adaptor synNotch and chimeric antigen receptors (CARs) for programmable antigen-targeting
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsJason Jakob Lohmueller, Alexander Deiters
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Abstract
Disclosed are compositions and methods related to the construction and use of universal synthetic notch (synNotch) receptors and chimeric antigen receptor (CAR) T cells.
Claims10
A universal chimeric antigen receptor (CAR), wherein the CAR comprises an adaptor molecule, a CD8α hinge domain, and a CD3ζ signaling domain, wherein the adaptor molecule comprises a modified O-6-methylguanine-DNA methyltransferase (protein SNAP-tag) that reacts specifically with O6-benzylguanine (BG), and wherein the protein SNAP-tag is covalently linked to an antibody or antigen-binding fragment thereof comprising one or more BGs.
A method of treating a cancer in a subject comprising administering to the subject
- a CAR T cell comprising a universal chimeric antigen receptor (CAR), wherein the CAR comprises an adaptor molecule, a CD8& hinge domain, and a CD35 signaling domain, wherein the adaptor molecule comprises a first modified O-6-methylguanine-DNA methyltransferase (protein SNAP-tag) that reacts specifically with O6-benzylguanine (BG) and wherein the first protein SNAP-tag is covalently linked to an antibody or antigen-binding fragment thereof comprising one or more BGs, wherein the antibody or antigen binding fragment thereof comprises rituximab, trastuzumab, or cetuximab.
Dependencies are inferred from the claim text.