IP Library Granted Patent US 12,540,170
Granted Patent B2
US 12,540,170 · App. 17/264,990 · Granted Feb 3, 2026

Chemokine responsive activated natural killer cells with secondary homing activation for verified targets

Inventors: Nathan Schomer (San Diego, CA); Laurent Boissel (San Diego, CA); Hans Klingemann (San Diego, CA)
Assignee: ImmunityBio, Inc.
C07K14/7158A61K40/15A61K40/31A61K40/4211A61K40/4219A61K40/4236C07K14/521C12N5/0646A61K2239/48
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,540,170
App. No.
17/264,990
Granted
Feb 3, 2026
Kind
B2
Abstract

Provided herein are modified NK-92 cells comprising a nucleic acid encoding C-C chemokine receptor type 7 (CCR7) operably linked to a promoter. Optionally, the cells further comprise a nucleic acid encoding C-C motif ligand 21 (CCL21), a nucleic acid encoding C-C motif ligand 19 (CCL19) or a combination thereof. Also provided are compositions and kits comprising the modified NK-92 cells. Provided are methods of making the modified cells and methods of treating cancer using the cells.

Claims (8)

1 . A modified NK-92 cell comprising (i) a nucleic acid encoding C-C chemokine receptor type 7 (CCR7) operably linked to a promoter, and (ii) a nucleic acid encoding C-C motif ligand 21 (CCL21) operably linked to a promoter,

wherein the promoter operably linked to CCL21 comprises one or more NFAT binding elements SEQ ID NO:4 and a minimal promoter SEQ ID NO:5, and has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:6.

2 . The modified NK-92 cell of claim 1 , wherein the nucleic acid encoding CCR7 has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:1.

3 . The modified NK-92 cell of claim 1 , wherein the nucleic acid encoding CCL21 has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO:2.

4 . The modified NK-92 cell of claim 1 , wherein the modified NK-92 cell further comprises a nucleic acid encoding C-C motif ligand 19 (CCL19).

5 . The modified NK-92 cell of claim 4 , wherein the nucleic acid encoding CCL19 is linked to the nucleic acid encoding CCL21 by a 2A peptide linker and wherein the same promoter drives expression of CCL19 and CCL21.

6 . A composition comprising the NK-92 cell of claim 1 and a pharmaceutically acceptable excipient.

7 . A kit comprising the NK-92 cell of claim 1 and instructions for use.

Assignments (4)
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 2, 2021
From: NANTKWEST, INC.
To: IMMUNITYBIO, INC.
Reel/Frame 057059/0802 →
CORRECTIVE ASSIGNMENT TO CORRECT THE PRIORITY 62539701 IN THE ASSIGNMENT DOCUMENT PREVIOUSLY RECORDED AT REEL: 056332 FRAME: 0686. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT . Recorded Jul 22, 2021
From: SCHOMER, NATHAN; BOISSEL, LAURENT; KLINGEMANN, HANS
To: NANTKWEST, INC.
Reel/Frame 056963/0658 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2021
From: SCHOMER, NATHAN; BOISSEL, LAURENT; KLINGEMANN, HANS
To: NANTKWEST, INC.
Reel/Frame 056332/0686 →
Continuity (1)
Related Publication 20210324042A1 · Oct 21, 2021
References Cited (40)
US 7098008B2 · Park et al. · 2006 [cited by applicant]
US 20020068044A1 · Klingemann · 2002 [cited by applicant]
US 20060222654A1 · Delcayre et al. · 2006 [cited by applicant]
US 20110206759A1 · Swartz · 2011 [cited by examiner]
US 20130189268A1 · Du et al. · 2013 [cited by applicant]
US 20130280285A1 · Schönfeld et al. · 2013 [cited by applicant]
US 20140242701A1 · Shiku et al. · 2014 [cited by applicant]
US 20140274909A1 · Orentas et al. · 2014 [cited by applicant]
CN 1629285A · 2005 [cited by applicant]
WO 199849268A1 · 1998 [cited by applicant]
WO 1999024566A1 · 1999 [cited by applicant]
WO 2000020460A1 · 2000 [cited by applicant]
WO 2014039523A1 · 2014 [cited by applicant]
WO 2014099671A1 · 2014 [cited by applicant]
WO WO2016044605A1 · 2016 [cited by examiner]
WO WO2016077734A2 · 2016 [cited by examiner]
WO 2018045177A1 · 2018 [cited by applicant]
Klingemann, H., Boissel, L., & Toneguzzo, F. (2016). Natural killer cells for immunotherapy-advantages of the NK-92 cell line over blood NK cells. Frontiers in immunology, 7, 91. (Year: 2016). [cited by examiner]
Ng et al, Predicting the Effects of Amino Acid Substitutions on Protein Function, Annual Review Genomics Human Genetics 7: 61-80, 2006 (Year: 2006). [cited by examiner]
https://www.calculator.net/exponent-calculator.html; last visited Dec. 23, 2024 (Year: 2024). [cited by examiner]
Examiner's Report, dated Feb. 25, 2022, CA Patent Application No. 3,107,101, 4 pages. [cited by applicant]
Notice of Reasons for Rejection, dated Apr. 26, 2022, JP Patent Application No. 2021-505220, 9 pages. [cited by applicant]
International Search Report and Written Opinion from PCT/US2018/044842, dated Apr. 17, 2019, 14 pages. [cited by applicant]
Klingemann, et al., “Natural Killer Cells for Immunotherapy—Advantages of the NK-92 Cell Line over Blood NK Cells,” Frontiers in Immunology, 2016, vol. 7, 91, 7 pages. [cited by applicant]
Carlsten, et al., “Efficient mRNA-Based Genetic Engineering of Human NK Cells with High-Affinity CD16 and CCR7 Augments Rituximab-Induced ADCC against Lymphoma and Targets NK Cell Migration toward the Lymph Node-Associa… [cited by applicant]
Somanchi, et al., “Engineering lymph node homing of ex vivo-expanded human natural killer cells via trogocytosis of the chemokine receptor CCR7,” Blood, 2012, vol. 119, No. 22, pp. 5164-5172. [cited by applicant]
Carlsten, et al., “Genetic manipulation of NK cells for cancer immunotherapy: techniques and clinical implications,” Frontiers in Immunology, 2015, vol. 6, Article 266, 9 pages. [cited by applicant]
Raju, et al., “Differential ligand-signaling network of CCL19/CCL21-CCR7 system,” Database: The Journal of Biological Database and Curation, 2015, vol. 2015, 6 pages. [cited by applicant]
Boissel, et al., “NK-92: An “Off the shelf” Target-Specific Cytotoxic Cell Therapeutic,” Cytotherapy, 2015, vol. 17, No. issue 6 supplement, 1 page. [cited by applicant]
Tonn, et al., “Treatment of patients with advanced cancer with the natural killer cell line NK-92,” Cytotherapy, 2013, vol. 15, No. 12, pp. 1563-1570. [cited by applicant]
Montaldo, et al., “Human NK Cell Receptors/Markers: A Tool to Analyze NK Cell Development, Subsets and Function,” Cytometry Part A, 2013, 83A, No. 8, pp. 702-713. [cited by applicant]
Gong, et al., “Characterization of a Human Cell Line (NK-92) with Phenotypical and Functional Characteristics of Activated Natural Killer Cells, ” Leukemia, 8:652-8 (1994). [cited by applicant]
Maki, et al., “Factors Regulating the Cytotoxic Activity of the Human Natural Killer Cell Line,” J Hematother Stem Cell Res., 10:369-83 (2001). [cited by applicant]
Suck et al., “NK-92: an ‘off-the-shelf therapeutic’ for adoptive natural killer cell-based cancer immunotherapy,” Cancer Immunol. Immunother. 65(4):485-92 (2016). [cited by applicant]
Klingemann, et al., “Purging of malignant cells from blood after short ex vivo incubation with NK-92 cells,” Blood, 87(11):4913-4 (1996). [cited by applicant]
Swift, et al., “Natural killer cell lines preferentially kill clonogenic multiple myeloma cells and decrease myeloma engraftment in a bioluminescent xenograft mouse model,” Haematologica. 97(7):1020-8 (2012). [cited by applicant]
Yan, et al., “Antileukemia Activity of a Natural Killer Cell Line against Human Leukemias,” Clin Cancer Res. 4:2859-68 (1998). [cited by applicant]
Tam, et al. “Immunotherapy of Malignant Melanoma in a SCID Mouse Model Using the Highly Cytotoxic Natural Killer Cell Line NK-92,” J Hematother. 8:281-90 (1999). [cited by applicant]
Konstantinidis et al “Targeting IL-2 to the endoplasmic reticulum confines autocrine growth stimulation to NK-92 cells” Exp Hematol. Feb. 2005;33(2):159-64. [cited by applicant]
Chinese Patent Application No. 201880096201.2, “First Office Action and Search Report,” dated Jan. 29, 2024, 18 pages. [cited by applicant]