US 12,258,381 B2
Activating chimeric receptors and uses thereof in natural killer cell immunotherapy
See Voon Seow, Singapore (SG); and Dario Campana, Singapore (SG)
Assigned to National University of Singapore, Singapore (SG)
Appl. No. 16/967,881
Filed by National University of Singapore, Singapore (SG)
PCT Filed Feb. 7, 2019, PCT No. PCT/IB2019/000181
§ 371(c)(1), (2) Date Aug. 6, 2020,
PCT Pub. No. WO2019/155288, PCT Pub. Date Aug. 15, 2019.
Claims priority of provisional application 62/736,879, filed on Sep. 26, 2018.
Claims priority of provisional application 62/628,788, filed on Feb. 9, 2018.
Prior Publication US 2021/0046115 A1, Feb. 18, 2021
Int. Cl. C07K 14/705 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); C07K 14/725 (2006.01); C12N 5/0783 (2010.01); C12N 15/113 (2010.01); C12N 15/62 (2006.01)
CPC C07K 14/70517 (2013.01) [A61K 39/4613 (2023.05); A61K 39/4631 (2023.05); A61K 39/464402 (2023.05); A61P 35/00 (2018.01); C07K 14/7051 (2013.01); C07K 14/7056 (2013.01); C07K 14/70578 (2013.01); C12N 5/0646 (2013.01); C12N 15/113 (2013.01); C12N 15/62 (2013.01); A61K 2239/38 (2023.05); A61K 2239/50 (2023.05); C07K 2319/03 (2013.01); C07K 2319/33 (2013.01); C12N 2310/14 (2013.01); C12N 2310/531 (2013.01)] 17 Claims
 
1. A population of Natural Killer (NK) cells expressing a first chimeric receptor and a second chimeric receptor, wherein:
a) the first chimeric receptor comprises an extracellular receptor domain, wherein said extracellular receptor domain comprises an engineered Natural Killer Group 2 member C (NKG2C) variant that comprises the amino acid sequence of SEQ ID NO. 64; and
b) the second chimeric receptor comprises an extracellular receptor domain, wherein said extracellular receptor domain comprises an engineered variant of Natural Killer Group 2 member A (NKG2A),
wherein the engineered variant of NKG2A is coupled to an effector domain comprising a transmembrane region and an intracellular signaling domain,
wherein the engineered NKG2A variant consists of the amino acid sequence of SEQ ID NO. 66.