IP Library › Granted Patent US 12,351,617
Granted Patent B2
US 12,351,617 · App. 17/740,899 · Granted Jul 8, 2025

Immune cells comprising truncated NKG2D chimeric receptors

Inventors: Jun Hao Leong (Singapore, SG); Noriko Shimasaki (Singapore, SG); See Voon Seow (Singapore, SG); Dario Campana (Singapore, SG); James Barnaby Trager (Albany, CA); Alexandra Leida Liana Lazetic (San Jose, CA); Chao Guo (San Francisco, CA); Luxuan Guo Buren (San Francisco, CA); Shyam Sashikant Masrani (London, GB)
Assignees: National University of Singapore; Nkarta, Inc.
C07K14/7056C07K14/5443C07K14/7051C07K14/70517C12N15/625C07K14/70578C07K2317/24C07K2317/53C07K2319/02C07K2319/03C07K2319/33
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Quick Facts
Patent No.
US 12,351,617
App. No.
17/740,899
Granted
Jul 8, 2025
Kind
B2
Abstract

Several embodiments disclosed herein relate to the compositions comprising engineered Natural Killer (NK) cells that express a chimeric receptor, the chimeric receptor imparting to the NK cells an enhanced ability to target specific cells, such as cancerous cells or those affected by an infectious disease. Several embodiments relate to NK cells that target cells expressing natural ligands of NKG2D, where the NK cells comprise transmembrane and/or signaling domains that lead to cytotoxic and/or cytolytic effects when the NK cells bind a target cell. Uses of NK cell compositions to treat diseases are also provided for in several embodiments.

Claims (12)

1. A natural killer (NK) cell expressing a chimeric receptor, the chimeric receptor comprising:

(a) an extracellular receptor domain comprising a fragment of Natural Killer Group 2 member D (NKG2D) that binds native ligands of NKG2D; and

(b) an effector domain comprising a transmembrane region and an intracellular signaling domain,

wherein the transmembrane region comprises a CD8α transmembrane domain, and the intracellular signaling domain comprises an OX-40 domain and CD3zeta, and

wherein the chimeric receptor comprises the amino acid sequence of SEQ ID NO: 109.

2. The NK cell of claim 1 , wherein the fragment of NKG2D is encoded by SEQ ID NO:2.

3. The NK cell of claim 1 , wherein CD3zeta is encoded by SEQ ID NO:13.

4. The NK cell of claim 2 , wherein CD3zeta is encoded by SEQ ID NO: 13.

5. The NK cell of claim 1 , wherein the NK cell expresses a membrane-bound interleukin-15 (mbIL15).

6. The NK cell of claim 5 , wherein the mbIL15 comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of SEQ ID NO: 17.

7. The NK cell of claim 5 , wherein the mbIL15 comprises the amino acid sequence of SEQ ID NO:17.

8. The NK cell of claim 5 , wherein the chimeric receptor and the mbIL15 are bicistronically expressed from a polynucleotide.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2022
From: LEONG, JUN HAO; SHIMASAKI, NORIKO; SEOW, SEE VOON; CAMPANA, DARIO
To: NATIONAL UNIVERSITY OF SINGAPORE
Reel/Frame 059885/0212 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 10, 2022
From: TRAGER, JAMES BARNABY; LAZETIC, ALEXANDRA LEIDA LIANA; GUO, CHAO; BUREN, LUXUAN GUO; MASRANI, SHYAM SASHIKANT
To: NKARTA, INC.
Reel/Frame 059885/0224 →
Continuity (4)
Continuation 16497678
Provisional Application 62628774 · Feb 9, 2018
Provisional Application 62477335 · Mar 27, 2017
Related Publication 20230002471A1 · Jan 5, 2023
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