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US 12,534,509 B2Granted
Engineered immune cells with receptor cross-talk
AssigneeA2 Biotherapeutics, Inc.
InventorAlexander Kamb
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Abstract
The present disclosure provides engineered immune cells and methods for their creation and use. The immune cells comprise activating and blocking receptors, that exhibit cross-talk between the receptors.
Claims20
An engineered immune cell comprising:
- an activating receptor that triggers a cytotoxic signal that promotes a cytotoxic response of the engineered immune cell when the activating receptor binds a first ligand of a target cell;
- and
- a blocking receptor that sends an interfering signal that inhibits the cytotoxic response of the engineered immune cell when the blocking receptor binds a second ligand of the target cell, said blocking receptor comprising a hinge domain that comprises a peptide comprising at least 24 contiguous amino acids from a leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) protein, wherein cross-talk between the activating receptor and the blocking receptor affects an activation threshold for the cytotoxic response.
A method for treating cancer, the method comprising:
- providing an engineered immune cell to a patient, wherein the engineered immune cell comprises an activating receptor and a blocking receptor, each expressed on a surface of the engineered immune cell, wherein:
- the activating receptor triggers a cytotoxic signal that promotes a cytotoxic response of the engineered immune cell when the activating receptor binds a first ligand of a target cell;
- and
- the blocking receptor sends an interfering signal that inhibits the cytotoxic response of the engineered immune cell when the blocking receptor binds a second ligand of the target cell, said blocking receptor comprising a hinge domain that comprises a peptide comprising at least 24 contiguous amino acids from a leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) protein, wherein cross-talk between the activating receptor and the blocking receptor affects an activation threshold for the cytotoxic response.
1 more element
A method of producing an engineered immune cell, the method comprising:
- determining an amount of cross-talk between an activating receptor and a blocking receptor for an engineered immune cell, wherein the amount of cross-talk between the activating receptor and the blocking receptor affects an activation threshold for the cytotoxic response;
- and
- producing an engineered immune cell that expresses different concentrations of the activating receptor and the blocking receptor based on the determined amount of cross-talk between the activating receptor and the blocking receptor, each said blocking receptor comprising a hinge domain that comprises a peptide comprising at least 24 contiguous amino acids from a leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) protein.
Dependencies are inferred from the claim text.