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US 12,595,291 B2Granted
Engineered immune cells with micro-clusters
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, which form into micro-clusters upon contacting a target or non-target cell.
Claims16
An engineered immune cell comprising:
- activating and blocking receptors on a surface of the engineered immune cell, wherein:
- when the engineered immune cell encounters a tumor cell, a first plurality of the activating receptors diffuse into a first region on the surface of the engineered immune cell and form a first micro-cluster proximal to the tumor cell that promotes a cytotoxic response by the engineered immune cell that results in cytotoxic effects on the tumor cell;
- and
- when the engineered immune cell encounters a normal cell, a second plurality of the activating and blocking receptors diffuse into a second region on the surface of the engineered immune cell and form a second micro-cluster proximal to the normal cell, wherein the blocking receptors in the second micro-cluster inhibit cytotoxic effects on the normal cell,
- wherein the activating receptors in the first micro-cluster bind to cognate activating ligands on the tumor cell, and the activating and blocking receptors in the second micro-cluster bind to cognate activating and blocking ligands on the normal cell,
- wherein the immune cell expresses different concentrations of the activating and blocking receptors and the ratio of the concentration of blocking receptors to activating receptors expressed by the immune cell is less than 1.
3 more elements
A method for treating cancer, the method comprising:
- providing an engineered immune cell to a patient, the engineered immune cell comprising activating and blocking cell-surface receptors, wherein:
- when the engineered immune cell encounters a normal cell, a first plurality of the activating and blocking receptors collect into a micro-cluster within a region of the cell-surface of the engineered immune cell proximal to the normal cell, wherein binding of one of the blocking receptors in the micro-cluster to a blocking ligand on the normal cell inhibits breakup of the micro-cluster, and wherein the engineered immune cell kills tumor cells that exhibit an activating ligand bound by the activating receptor and do not exhibit the blocking ligand such that the blocking receptor remains unbound,
- wherein the immune cell expresses different concentrations of the activating and blocking receptors and the ratio of the concentration of blocking receptors to activating receptors expressed by the immune cell is less than 1.
Dependencies are inferred from the claim text.