Granted Patent
B2
US 12,435,122 · App. 17/056,385 · Granted Oct 7, 2025
Fc-epsilon CAR
Inventors:
Laurent H. Boissel (San Diego, CA); Hans G. Klingemann (San Diego, CA); Abhijit Dandapat (San Diego, CA); Himani Chinnapen (San Diego, CA)
Assignee:
ImmunityBio, Inc.
C07K14/70535A61K38/1774A61K38/2013A61K38/2086A61K39/3955A61K39/39558A61K40/15A61K40/31A61K40/4203A61K40/4204A61K40/4205A61K40/421A61K40/4211A61K40/4215A61K40/4217A61K40/4221A61K40/4224A61K40/4249A61K40/4261A61K40/46A61K45/06A61P35/00C07K14/5443C07K14/55C07K14/70517C07K14/70521C07K16/2803C07K16/2827C07K16/2863C07K16/2866C07K16/2878C07K16/32C12N5/0646A61K2039/505A61K2239/22A61K2239/31A61K2239/38A61K2239/48A61K2239/49A61K2239/55C07K2317/53C07K2317/622C07K2317/76C07K2319/02C07K2319/03C07K2319/30C07K2319/33C12N2510/00
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Abstract
Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK/NK-92 cells.
Claims (15)
1. A genetically modified NK cell, comprising:
a cytokine;
a CD16; and
a membrane bound chimeric antigen receptor (CAR) that comprises a FcεRIγ signaling domain having the amino acid sequence of SEQ ID NO:1; and
wherein the CAR is
a CD19-CAR having the amino acids 1-407 of SEQ ID NO:29,
a PD-L1-CAR encoded by a nucleic acid sequence of SEQ ID NO:42, or
a B7-H4-CAR encoded by a nucleic acid sequence of SEQ ID NO:45.
2. The genetically modified NK cell of claim 1 , wherein the NK cell is an NK-92 cell.
3. The genetically modified NK cell of claim 1 , wherein the cytokine is IL-2.
4. The genetically modified NK cell of claim 1 , wherein the cytokine comprises an endoplasmic retention sequence.
5. The genetically modified NK cell of claim 1 , wherein the CD16 is a high-affinity CD16 variant having the amino acid sequence of SEQ ID NO: 35 and having a 158V mutation.
6. The genetically modified NK cell of claim 1 , wherein the genetically modified NK cell comprises a tricistronic nucleic acid sequence comprising a sequence encoding the cytokine, a sequence encoding the CD16, and a sequence encoding the CAR.
7. The genetically modified NK cell of claim 6 , wherein the tricistronic nucleic acid sequence is integrated into the genome of the NK cell.
8. The genetically modified NK cell of claim 1 , wherein the cytokine is IL-15.
Assignments (3)
SECURITY INTEREST
Recorded Jan 2, 2024
From: IMMUNITYBIO, INC.; NANTCELL, INC.; RECEPTOME, INC.; VBC HOLDINGS LLC; ALTOR BIOSCIENCE, LLC; ETUBICS CORPORATION; IGDRASOL, INC.
To: INFINITY SA LLC, AS PURCHASER AGENT
Reel/Frame 066179/0074 →
CHANGE OF NAME
Recorded Aug 18, 2021
From: NANTKWEST, INC.
To: IMMUNITYBIO, INC.
Reel/Frame 057319/0192 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Aug 4, 2021
From: BOISSEL, LAURENT H.; KLINGEMANN, HANS G.; DANDAPAT, ABHIJIT; CHINNAPEN, HIMANI
To: NANTKWEST, INC.
Reel/Frame 057079/0608 →
Continuity (2)
Provisional Application
62674936
· May 22, 2018
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