US 12,012,612 B2
Engineered immune cells with receptor signal strength modulated by a hinge
Alexander Kamb, Agoura Hills, CA (US)
Assigned to A2 BIOTHERAPEUTICS, INC., Agoura Hills, CA (US)
Filed by A2 BIOTHERAPEUTICS, INC., Agoura Hills, CA (US)
Filed on Sep. 21, 2021, as Appl. No. 17/480,490.
Claims priority of provisional application 63/081,256, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,237, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,248, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,242, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,258, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,231, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,229, filed on Sep. 21, 2020.
Claims priority of provisional application 63/081,250, filed on Sep. 21, 2020.
Prior Publication US 2022/0089676 A1, Mar. 24, 2022
Int. Cl. C07K 14/725 (2006.01); A61K 35/17 (2015.01); C07K 14/47 (2006.01); C12N 5/0783 (2010.01); C12N 15/85 (2006.01)
CPC C12N 5/0637 (2013.01) [A61K 35/17 (2013.01); C07K 14/4702 (2013.01); C07K 14/7051 (2013.01); C12N 15/85 (2013.01); C07K 2317/53 (2013.01); C07K 2317/622 (2013.01); C07K 2319/03 (2013.01); C07K 2319/715 (2013.01); C12N 2510/00 (2013.01)] 13 Claims
 
1. A method of producing an engineered immune cell, the method comprising:
determining a strength of a blocking signal sent from a cell surface blocking receptor caused to be expressed on an engineered immune cell from an introduced vector encoding said blocking receptor, said strength determined at least in-part due to a length of a hinge of the cell surface blocking receptor, wherein the length of the hinge is known, wherein a longer hinge lengths impart an increased blocking signal strength of the cell surface blocking receptor,
wherein the hinge comprises a peptide derived from leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) of between 10 and 64 amino acids in length; and
producing an engineered immune cell that expresses the cell surface blocking receptor having the hinge with a known length and a cell surface activating receptor that sends an activating signal that promotes a cytotoxic response and that is inhibited by the blocking signal,
said blocking and activating receptor each expressed from an introduced vector encoding the receptor and each receptor comprising an extracellular binding domain, a hinge, a transmembrane domain, and an intracellular domain.