Granted Patent
B2
US 12,203,065 · App. 16/613,601 · Granted Jan 21, 2025
Method for culturing natural killer cell, using transformed T cell
Inventors:
Bokyung Min (Yongin-si, KR); Gyeong Min PArk (Yongin-si, KR); Hyun Ah Kim (Yongin-si, KR); Bitna Yang (Yongin-si, KR); Yu Kyeong Hwang (Yongin-si, KR); Hyojin Kim (Yongin-si, KR)
Assignee:
GC Cell Corporation
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Abstract
A method for culturing natural killer cells uses genetically modified T cells. The method for culturing natural killer cells, using genetically modified T cells enables the effective proliferation and production of natural killer cells from a smaller amount of source cells. In addition, the method enhances the cytolytic activity of natural killer cells. Therefore, the method for culturing natural killer cells, using genetically modified T cells may be suitable for various applications in commercializing cell therapy products. Further, the natural killer cells produced by the culturing method can be useful as a cell therapy product.
Claims (30)
1. A genetically modified CD4+T cell that expresses a TNF-α gene mutated to encode an amino acid other than Alanine at the amino acid corresponding to P76 of SEQ ID NO: 8 and/or an amino acid other than Valine at the amino acid corresponding to V77 of SEQ ID NO: 8; wherein the cell is inactivated.
2. The genetically modified CD4+T cell of claim 1 , wherein the CD4+T cell is a Hut78, H9, or Jurkat cell.
3. The genetically modified CD4+T cell of claim 1 , wherein the CD4+T cell is a Hut78 cell.
4. The genetically modified CD4+T cell of claim 1 , wherein the TNF-α gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 8.
5. The genetically modified CD4+T cell of claim 1 , wherein the cell further expresses a membrane-bound IL-21 gene.
6. The genetically modified CD4+T cell of claim 5 , wherein the membrane-bound IL-21 gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 3.
7. The genetically modified CD4+T cell of claim 1 , wherein the cell further expresses a 4-1BBL gene.
8. The genetically modified CD4+T cell of claim 7 , wherein the 4-1BBL gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 1.
9. The genetically modified CD4+T cell of claim 1 , wherein the cell further expresses an OX40L gene.
10. The genetically modified CD4+T cell of claim 9 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
11. The genetically modified CD4+T cell of claim 5 , wherein the cell further expresses a 4-1BBL gene.
12. The genetically modified CD4+T cell of claim 11 , wherein the 4-1BBL gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 1.
13. The genetically modified CD4+T cell of claim 6 , wherein the cell further expresses a 4-1BBL gene.
14. The genetically modified CD4+T cell of claim 13 , wherein the 4-1BBL gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 1.
15. The genetically modified CD4+T cell of claim 5 , wherein the cell further expresses an OX40L gene.
16. The genetically modified CD4+T cell of claim 15 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
17. The genetically modified CD4+T cell of claim 6 , wherein the cell further expresses an OX40L gene.
18. The genetically modified CD4+T cell of claim 17 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
19. The genetically modified CD4+T cell of claim 7 , wherein the cell further expresses an OX40L gene.
20. The genetically modified CD4+T cell of claim 19 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
21. The genetically modified CD4+T cell of claim 8 , wherein the cell further expresses an OX40L gene.
22. The genetically modified CD4+T cell of claim 21 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
23. The genetically modified CD4+T cell of claim 11 , wherein the cell further expresses an OX40L gene.
24. The genetically modified CD4+T cell of claim 23 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
25. The genetically modified CD4+T cell of claim 12 , wherein the cell further expresses an OX40L gene.
26. The genetically modified CD4+T cell of claim 25 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
27. The genetically modified CD4+T cell of claim 13 , wherein the cell further expresses an OX40L gene.
28. The genetically modified CD4+T cell of claim 27 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
29. The genetically modified CD4+T cell of claim 14 , wherein the cell further expresses an OX40L gene.
30. The genetically modified CD4+T cell of claim 29 , wherein the OX40L gene comprises a nucleotide sequence encoding the amino acid of SEQ ID NO: 5.
Assignments (2)
MERGER AND CHANGE OF NAME
Recorded Mar 2, 2022
From: GREEN CROSS LAB CELL CORPORATION; GC CELL CORPORATION
To: GC CELL CORPORATION
Reel/Frame 059306/0334 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Nov 14, 2019
From: MIN, BOKYUNG; PARK, GYEONG MIN; KIM, HYUN AH; YANG, BITNA; HWANG, YU KYEONG; KIM, HYOJIN
To: GREEN CROSS LAB CELL CORPORATION
Reel/Frame 051012/0247 →
Priority Claims (1)
KR 10-2017-0065180
· May 26, 2017
· national
Continuity (1)
References Cited (231)
US 5882650A
· Ennis
· 1999
[cited by applicant]
US 9062287B2
· Ideno et al.
· 2015
[cited by applicant]
US 9834753B2
· Min et al.
· 2017
[cited by applicant]
US 20030068306A1
· Dilber
· 2003
[cited by applicant]
US 20080138833A1
· Braun et al.
· 2008
[cited by applicant]
US 20120045423A1
· Har-Noy
· 2012
[cited by applicant]
US 20130011376A1
· Peled et al.
· 2013
[cited by applicant]
US 20140050710A1
· Gonzalez et al.
· 2014
[cited by applicant]
US 20170319621A1
· Min et al.
· 2017
[cited by applicant]
US 20190037831A1
· Hwang et al.
· 2019
[cited by applicant]
US 20190336533A1
· Hwang et al.
· 2019
[cited by applicant]
US 20210147803A1
· Hwang et al.
· 2021
[cited by applicant]
US 20240050478A1
· Min et al.
· 2024
[cited by applicant]
CA 2977472
· 2016
[cited by applicant]
CN 102911918A
· 2013
[cited by applicant]
CN 103068973
· 2013
[cited by applicant]
CN 102112600
· 2014
[cited by applicant]
CN 102911918
· 2014
[cited by applicant]
CN 104204194
· 2014
[cited by applicant]
CN 104321425
· 2015
[cited by applicant]
CN 105602899
· 2016
[cited by applicant]
CN 106222141
· 2016
[cited by applicant]
CN 106222141A
· 2016
[cited by applicant]
CN 108300693
· 2018
[cited by applicant]
CN 108300697
· 2018
[cited by applicant]
EP 2856876
· 2015
[cited by applicant]
EP 3633029
· 2020
[cited by applicant]
JP 2004501110
· 2004
[cited by applicant]
JP 2008544760
· 2008
[cited by applicant]
JP 2010501173
· 2010
[cited by applicant]
JP 2010523083
· 2010
[cited by applicant]
JP 2011529341
· 2011
[cited by applicant]
JP 2012521215
· 2012
[cited by applicant]
JP 2013006793
· 2013
[cited by applicant]
JP 2013027385
· 2013
[cited by applicant]
JP 2013071915
· 2013
[cited by applicant]
JP 2015502756
· 2015
[cited by applicant]
JP 2015513403
· 2015
[cited by applicant]
JP 2018520993
· 2015
[cited by applicant]
JP 5840837
· 2016
[cited by applicant]
JP 5840837B2
· 2016
[cited by applicant]
JP 2017525370
· 2017
[cited by applicant]
JP 2018501779
· 2018
[cited by applicant]
JP 7039623
· 2022
[cited by applicant]
KR 1020080008060
· 2008
[cited by applicant]
KR 1020090121694
· 2009
[cited by applicant]
KR 1020100011586
· 2010
[cited by applicant]
KR 1020100012586
· 2010
[cited by applicant]
KR 101035556
· 2011
[cited by applicant]
KR 101133185
· 2011
[cited by applicant]
KR 1020110132618
· 2011
[cited by applicant]
KR 1020120091012
· 2012
[cited by applicant]
KR 101298012
· 2013
[cited by applicant]
KR 1020140123503
· 2014
[cited by applicant]
KR 101520534
· 2015
[cited by applicant]
KR 1020160063114
· 2016
[cited by applicant]
KR 1020160066837
· 2016
[cited by applicant]
KR 101644984
· 2016
[cited by applicant]
KR 101706524
· 2017
[cited by applicant]
WO WO9705239
· 1997
[cited by applicant]
WO WO1997032970
· 1997
[cited by applicant]
WO WO9806822
· 1998
[cited by applicant]
WO WO2005014637
· 2005
[cited by examiner]
WO WO2005007116
· 2006
[cited by applicant]
WO WO2007111677
· 2007
[cited by applicant]
WO WO2008023874
· 2008
[cited by applicant]
WO WO2008121420
· 2008
[cited by applicant]
WO WO2008133845
· 2008
[cited by applicant]
WO WO2008138214
· 2008
[cited by applicant]
WO WO2009060865
· 2009
[cited by applicant]
WO WO2009132192
· 2009
[cited by applicant]
WO WO2009132283A2
· 2009
[cited by examiner]
WO WO2009151183
· 2009
[cited by applicant]
WO WO2010013947
· 2010
[cited by applicant]
WO WO2010110734
· 2010
[cited by applicant]
WO WO2011080740
· 2011
[cited by applicant]
WO WO2013094988
· 2013
[cited by applicant]
WO WO2014188680
· 2014
[cited by applicant]
WO WO2015157386A1
· 2015
[cited by examiner]
WO WO2016069993
· 2016
[cited by examiner]
WO WO2016085248
· 2016
[cited by applicant]
WO WO2016154585
· 2016
[cited by applicant]
WO WO2016139463A1
· 2016
[cited by examiner]
WO WO2017135631
· 2017
[cited by applicant]
WO WO2018124766
· 2018
[cited by applicant]
WO WO2018197859
· 2018
[cited by applicant]
WO WO2018217064
· 2018
[cited by applicant]
WO WO2019098682
· 2019
[cited by applicant]
WO WO2019182392
· 2019
[cited by applicant]
WO WO2020055040
· 2020
[cited by applicant]
WO WO2020101361
· 2020
[cited by applicant]
WO WO2021235894
· 2021
[cited by applicant]
WO WO2022133056
· 2022
[cited by applicant]
WO WO2022133057
· 2022
[cited by applicant]
WO WO2022133061
· 2022
[cited by applicant]
WO WO2022216144
· 2022
[cited by applicant]
WO WO2022216811
· 2022
[cited by applicant]
WO WO2022216813
· 2022
[cited by applicant]
WO WO2022216815
· 2022
[cited by applicant]
WO WO2022216826
· 2022
[cited by applicant]
WO WO2022216831
· 2022
[cited by applicant]
WO WO2022216837
· 2022
[cited by applicant]
WO WO2023080895
· 2023
[cited by applicant]
WO WO2023081317
· 2023
[cited by applicant]
Hassell et al., “Adaptation to non-ammoniagenic medium and selective substrate feeding lead to enhanced yields in animal cell cultures,” Journal of Cell Science, Jul. 1990, 96(3):501-508.
[cited by applicant]
KR Office Action in Korean Appln. No. 10-2019-7030133, dated May 23, 2022, 9 pages (with English Translation).
[cited by applicant]
Condiotti, R., et al., “Ex Vivo Expansion of Cd56+ Cytotoxic Cells from Human Umbilical Cord Blood, ” Experimental Hematology 29(2001):104-113, Elsevier Science Inc, Netherlands (Jan. 2001).
[cited by applicant]
Denman, C.J., “Membrane-Bound II-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cells, ” PLoS One 7(1):e30264, Public Library of Science, United States (2012).
[cited by applicant]
Fujisaki, H., et al., “Expansion of Highly Cytotoxic Human Natural Killer Cells For Cancer Cell Therapy,” Cancer Research 69(9):4010-4017, American Association for Cancer Research, United States (May 2009).
[cited by applicant]
Gong, W., et al., “Ex Vivo Expansion of Natural Killer Cells With High Cytotoxicity By K562 Cells Modified to Co-Express Major Histocompatibility Complex Class I Chain-Related Protein A, 4-1BB Ligand, and Interleukin-15…
[cited by applicant]
Goodier, M.R and Londei, M, “Lipopolysaccharide Stimulates the Proliferation of Human Cd56+Cd3- Nk Cells: A Regulatory Role of Monocytes and II-10, ” Journal of Immunology 165(1):139-147, American Association of Immunol…
[cited by applicant]
Written Opinion for International Application No. PCT/KR2018/005983, Korean Intellectual Property Office, Republic of Korea, mailed on Feb. 8, 2019, 12 pages.
[cited by applicant]
Kim et al., “Engineering Conferences International ECI Digital Archives Scale-up study for ex-vivo expansion of allogeneic natural killer cells in stirred-tank bioreactor, Hyuang Jin nam Sang Hyun Lee Recommended Citati…
[cited by applicant]
Ando et al., “Extensive generation of human cord blood CD34 stem cells from Lin 2CD34 cells in a long-term in vitro system” Exp. Hematol., 2000 28:690-9.
[cited by applicant]
Bae et al., “Development of NK cell expansion methods using feeder cells from human myelogenous leukemia cell line,” Blood Research, Sep. 2014, 49(3):154-61.
[cited by applicant]
Baek et al., “Ex Vivo Expansion of Natural Killer Cells Using Cryopreserved Irradiated Feeder Cells,” Anticancer Res., Jan. 2013, 33:2011-2020.
[cited by applicant]
Berg et al., “Clinical Grade Ex Vivo-Expanded Human Natural Killer Cells Upregulate Activating Receptors and Death Receptor Ligands and Have Enhanced Cytolytic Activity against Tumor Cells,” Cytotherapy, 2009, 11(3):41-…
[cited by applicant]
Boissel et al., “Umbilical Cord Mesenchymal Stem Cells Increase Expansion of Cord Blood Natural Killer Cells,” Biology of Blood and Marrow Transplantation, Sep. 2008, 14(9):1031-8.
[cited by applicant]
Byers “What Can Randomized Controlled Trials Tell US About Nutrition and Cancer Prevention?,” Cancer Journal, 1999, 49(6):353-61.
[cited by applicant]
Carlens et al., “A New Method for In Vitro Expansion of Cytotoxic Human CD3-CD56+ Natural Killer Cells, ” Human Immunology, Oct. 2001, 62(10):1092-8.
[cited by applicant]
Castriconi et al., “Human NK cell infusions prolong survival of metastatic human neuroblastoma-bearing NOD/scid mice” Cancer Immunol. Immunother., Nov. 2007, 56(11):1733-42.
[cited by applicant]
Childs and Berg, “Bringing natural killer cells to the clinic: ex vivo manipulation,” Hematology Am. Soc. Hematol. Educ. Program, 2013. 2013(1):234-46.
[cited by applicant]
Condiotti et al., “Ex vivo expansion of CD56+ cytotoxic cells from human umbilical cord blood,” Experimental Hematol., 2001, 29(1):104-13.
[cited by applicant]
Dahlberg et al., “Natural Killer Cell-Based Therapies Targeting Cancer: Possible Strategies to Gain and Sustain Anti-Tumor Activity,” Front. Immunol., 2015, 6:1-19).
[cited by applicant]
Denman et al, “Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer Cell” PloSONE, 2012, 7(1):e30264.
[cited by applicant]
Dermer, “Another Anniversary for the War on Cancerm,” Bio/Technology, 1994, 12:320.
[cited by applicant]
Dewan et al., “Role of natural killer cells in hormone-independent rapid tumor formation and spontaneous metastasis of breast cancer cells in vivo” Breast Cancer Res. Treatment, 2007, 104(3):267-75.
[cited by applicant]
Dunne et al., “Selective Expansion and Partial Activation of Human NK Cells and NK Receptor-Positive T Cells by IL-2 and IL-15,” J. Immunol., 2001167(6):3129-38.
[cited by applicant]
Edwards et al., “The Remarkable Flexibility of the Human Antibody Repertoire; Isolation of Over One Thousand Different Antibodies to a Single Protein, BLyS,” JMB, 2003, 334:103-18.
[cited by applicant]
Extended European Search Report in European Appln. No. 18805231.0, dated May 7, 2021, 10 pages.
[cited by applicant]
Freshney, “Culture of Animal Cells, A Manual of Basic Technique,” Alan R. Liss, Inc., 1983, 1-4.
[cited by applicant]
Frias et al., “Generation of functional natural killer and dendritic cells in a human stromal-based serum-free culture system designed for cord blood expansion” Experimental Hematology, 2008, 36(1):61-8.
[cited by applicant]
Fujisaki et al., “Expansion of Highly Cytotoxic Human Natural Killer Cells for Cancer Cell Therapy,” Cancer Res., May 1, 2009,69(9):4010-7.
[cited by applicant]
GenBank Accesion No. CAA56284.1, “OX 40 ligand/ gp 34 [
[cited by applicant]
GenBank Accession No. LN874322.1, “TPA_inf:
[cited by applicant]
GenBank Accestion No. NM_001768.7, “
[cited by applicant]
GenBank Accestion No. NM_003326.5, “
[cited by applicant]
GenBank Accestion No. NM_003811.4, “
[cited by applicant]
GenBank Accestion No. NM_021803.3, “
[cited by applicant]
Goel et al., “Plasticity within the Antigen-Combining Site May Manifest as Molecular Mimicryin the Hurnoral Immune Response,” J. Immunol., 2004, 173:7358-67.
[cited by applicant]
Gong et al., “Ex vivo expansion of natural killer cells with high cytotoxicity by K562 cells modified to co express major histocompatibility complex class I chain-related protein A, 4-1 BB ligand, and interleukin-15,” T…
[cited by applicant]
Goodier et al., “Lipopolysaccharide Stimulates the Proliferation of Human CD56+CD3-NK Cells: A Regulatory Role of Monocytes and IL-10,” J. Immunology, 2000, 165(1):139-47.
[cited by applicant]
Holmes et al., “A Human NK Cell Activation/Inhibition Threshold Allows Small Changes in the Target Cell Surgace Phenotype to Dramatically Alter Susceptibility to NK Cells,” J. Immunol., 2011, 186:1538-45.
[cited by applicant]
iwai-chem.co.jp [online] “DataSheet: CellGro/CellGenix GMP Serum-free StemCell GrowthMedium (SCGM) Xeno-free”, May 16, 2011, via Internet Archive: Wayback Machine URL <https://web.archive.org/web/20140124200115/http://w…
[cited by applicant]
Kelly et al., “Memory CD4+ T Cells Are Required for Optimal NK Cell Effector Functions against the Opportunistic Fungal Pathogen Pneumocystis murina”, J. Immunology, 2013, 190:285-95.
[cited by applicant]
Keridiles et al., “T cell regulation of natural killer cells”, J. Experimental Medicine, Jun. 2013, 210(6):1065-8.
[cited by applicant]
Khan and Salunke, “Adjustable Locks and Flexible Keys: Plasticity of Epitope-Paratope Interactions in Germline Antibodies,” J. Immunol., 2014, 192(11):5398-405.
[cited by applicant]
Kim et al., “Ex vivo activation and expansion of natural killer cells from patients with advanced cancer with feeder cells from healthy volunteers”, Cytotherapy, 2013, 15:231-41.
[cited by applicant]
Koehl et al., “IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation, ” Blood Cells Molecules & Disease, Nov.-Dec. 2004, 33(3):261-6.
[cited by applicant]
Lim et al., “Ex Vivo Expansion of Highly Cytotoxic Human NK Cells by Cocultivation with Irradiated Tumor Cells for Adoptive Immunotherapy,” Cancer Res., Apr. 15, 2013, 73(8):2598-607.
[cited by applicant]
Lim et al., “GMP-Compliant, Large-Scale Expanded Allogeneic Natural Killer Cells Have Potent Cytolytic Activity against Cancer Cells In Vitro and In Vivo,” PlosOne, Jan. 2013, 8(1):1-9.
[cited by applicant]
Lloyd et al., “Modelling the human immune response: performance of a human antibody repertoire against a 10 broad panel of therapeutically relevant antigens,” Protein Engineering, Eng. Design & Selection, 2009, 22(3):15…
[cited by applicant]
Miller et al., “Role of monocytes in the expansion of human activated natural killer cells, ” Blood, Nov. 1992, 80(9):2221-9.
[cited by applicant]
Min, “Identification of NK cell costimulatory receptors for large-scale expansion of NK cells for adoptive immunotherapy in cancer patients ,” Thesis for the degree of Doctor ,2018, http://library.kaist.ac.kr/search/det…
[cited by applicant]
Mingari et al., “In Vitro Proliferation and Cloning of CD3-CD16+ Cells from Human Thymocyte Precursors”, J. Exp. Med., Jul. 1991, 174:21-6.
[cited by applicant]
Miyahira, “Types of Immune Cells Present in Human PBMC,” Sanguine Bio Researcher Blog, Nov. 22, 2012, 3 pages.
[cited by applicant]
Morris et al., “A high-efficiency system of natural killer cell cloning,” Journal of Immunological Methods,2005, 307(1-2):24-33.
[cited by applicant]
North et al., “Tumor-Primed Human Natural Killer Cells Lyse NK-Resistant Tumor Targets: Evidence of a Two-Stage Process in Resting NK Cell Activation,” J. Immunology, 2007, 178(1):85-94.
[cited by applicant]
PCT International Search Preliminary Report on Patentability in International Appln. No. PCT/KR2018/005983, dated Nov. 26, 2019, 13 pages.
[cited by applicant]
PCT International Search Report and Written Opinion in International Appln. No. PCT/KR2018/005983, dated Feb. 8, 2019, 17 pages.
[cited by applicant]
Perez et al., “A potential role for hydrocortisone in the positive regulation of IL-15-activated NK-cell proliferation and survival,” Blood, Jul. 2005, 106(1):158-66.
[cited by applicant]
Poggi et al., “Extrathymic differentiation of T lymphocytes and natural killer cells from human embryonic liver precursors”, Proc. Natl. Acad. Sci. USA, May 1993, 90:4465-9.
[cited by applicant]
Poosarla et al., “Computational De Novo Design of Antibodies Binding to a Peptide With High Affinity,” Biotechn. Bioeng., 2017, 114(6): 1331-42.
[cited by applicant]
Siegler et al., “Good manufacturing practice-compliant cell sorting and large-scale expansion of single KIR-positive alloreactive human natural killer cells for multiple infusions to leukemia patients,” Cytotherapy, 201…
[cited by applicant]
Sigmaaldrich.com, “Sigma-Aldrich H9”, retrieved on Nov. 15, 2019, retrieved from URL <https://www.sigmaaldrich.com/catalog/productUsigma/cb_85050301?1ang=en®ion=US&cm_sp=Insite -_- prodRecCold_xviews-_-prodRecCold10-…
[cited by applicant]
Torres and Casadevall, “The immunoglobulin constant region contributes to affinity and specificity,” Trend. Immunol., Jan. 2008, 29(2): 91-7.
[cited by applicant]
Vansdol et al., “Generation of Functional CD56+ Natural Killer (NK) Cells from Ex Vivo Expanded Human Cord Blood (CB) Hematopoietic Stem Cells”, Blood, 2000, Abstract#424, 96(11):128b.
[cited by applicant]
Vitale et al., “Effect of Tumor Cells and Tumor Microenvironment on NK-cell Function” Euro. J. Immunol., 2014, 44:1582-92.
[cited by applicant]
www.thermofisher.com [online] “CTS (TM) AIM V (R) Medium”, Aug. 24, 2015, retrieved from URL<http://www.thermofisher.com/order/catalog/product/0870112BK?ICID=search-product>, 4 pages.
[cited by applicant]
Xiao-Hong et al., “Ex vivo expansion of highly purified NK cells from human peripheral blood”, Zhongguo shi yan xue ye xue za zhi . . . , Apr. 2007, 15(2):373-7.
[cited by applicant]
Zips et al., “New AntiCancer Agents: In Vitro and In Vivo Evaluation” In vivo, 2005, 19:1-8.
[cited by applicant]
Ncbi, NCBI Reference Sequence No. LN874322.1, Jun. 8, 2016, 3 pages.
[cited by applicant]
NCBI, NCBI Reference Sequence No. CAA56284.1, Oct. 7, 2008, 2 pages.
[cited by applicant]
Duk Seong Bae et al., “Development of NK cell expansion methods using feeder cells from human myelogenous leukemia cell line,” Blood Research, Sep. 2014, pp. 154-161 (9 pages), vol. 49, No. 3.
[cited by applicant]
International Search Report of PCT/KR2018/005983 dated Feb. 8, 2019.
[cited by applicant]
KR Office Action in Korean Application No. 10-2019-7030133, dated Jan. 19, 2022, 6 pages (with English translation).
[cited by applicant]
Park et al., “CD4 T-cells transduced with CD80 and 4-1BBL mRNA induce long-term CD8 T-cell responses resulting in potent antitumor effects,” Vaccine, Nov. 2014, 32: 6919-6926.
[cited by applicant]
Ahn et al., “Irradiated and Activated Autologous PBMCs Induce Expansion of Highly Cytotoxic Human NK Cells In Vitro,” Journal of Immunotherapy, Sep. 2013, 36(7):373-381.
[cited by applicant]
Almishri et al., “TNFα augments cytokine-induced NK Cell IFNγ production through TNFR2,” Journal of Innate Immunity, 2016, 8(6):617-629.
[cited by applicant]
Carson et al., “A potential role for interleukin-15 in the regulation of human natural killer cell survival.,” The Journal of Clinical Investigation, Mar. 1, 1997, 99(5):937-943.
[cited by applicant]
Choi et al., “Donor-Derived Natural Killer Cells Infused after Human Leukocyte Antigen-Haploidentical Hematopoietic Cell Transplantation: A Dose-Escalation Study,” Biology of Blood and Marrow Transplantation, 2014, 20(5…
[cited by applicant]
Croft, “Control of immunity by the TNFR-related molecule OX40 (CD134),” Annual Review of Immunology, 2010, 28(1):57-78.
[cited by applicant]
Granzin et al., “Shaping of Natural Killer Cell Antitumor Activity by Ex Vivo Cultivation,” Frontiers in Immunology, Apr. 26, 2017, 8:458, 18 pages.
[cited by applicant]
Lee et al., “Expansion of cytotoxic natural killer cells using irradiated autologous peripheral blood mononuclear cells and anti-CD16 antibody,” Scientific Reports, Sep. 11, 2017, 7(1):1-13.
[cited by applicant]
Mason et al., “Regulation of NK cells through the 80-kDa TNFR (CD120b),” Journal of Leukocyte Biology, Aug. 1, 1995, 58(2):249-255.
[cited by applicant]
Min et al., “Harnessing novel engineered feeder cells expressing activating molecules for optimal expansion of NK cells with potent antitumor activity,” Cellular & Molecular Immunology, Sep. 27, 2021, 19(2):296-298.
[cited by applicant]
Min et al., “Optimization of Large-Scale Expansion and Cryopreservation of Human Natural Killer Cells for Anti-Tumor Therapy,” Immune Network, Jan. 1, 20118, 18(4):e31, 13 pages.
[cited by applicant]
Parkhurst et al., “Adoptive Transfer of Autologous Natural Killer Cells Leads to High Levels of Circulating Natural Killer Cells but Does Not Mediate Tumor Regression,” Clinical Cancer Research, Oct. 1, 2011, 17(19):628…
[cited by applicant]
Parrish-Novak et al., “Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function,” Nature, Nov. 2, 2000, 408(6808):57-63.
[cited by applicant]
Parrish-Novak et al., “Interleukin-21 and the IL-21 receptor: novel effectors of NK and T cell responses,” Journal of Leukocyte Biology, Nov. 1, 2002, 72(5):856-863.
[cited by applicant]
Sakamoto et al., “Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer,” Journal of Translational Medicine, Aug. 25, 2015, 13:277, 13 pages.
[cited by applicant]
Shuford et al., “4-1BB Costimulatory Signals Preferentially Induce CD8+ T Cell Proliferation and Lead to the Amplification In Vivo of Cytotoxic T Cell Responses,” The Journal of Experimental Medicine, Jul. 7, 1997, 186(…
[cited by applicant]
Turaj et al., “Augmentation of CD134 (OX40)-dependent NK anti-tumour activity is dependent on antibody cross-linking,” Scientific Reports, Feb. 2018, 8(1):1-11.
[cited by applicant]
Wendt et al., “Interleukin-21 differentially affects human natural killer cell subsets,” Immunology, Dec. 2007, 122(4):486-495.
[cited by applicant]
Wilcox et al., “Signaling through NK cell-associated CD137 promotes both helper function for CD8+ cytolytic T cells and responsiveness to IL-2 but not cytolytic activity,” The Journal of Immunology, Oct. 15, 2002, 169(8…
[cited by applicant]
Willoughby et al., “OX40: Structure and function—What questions remain?,” Molecular Immunology, Mar. 2017, 83:13-22.
[cited by applicant]
Xu et al., “Essential role of the TNF-TNFR2 cognate interaction in mouse dendritic cell-natural killer cell crosstalk,” Blood, Apr. 15, 2007, 109(8):3333-3341.
[cited by applicant]
Yang et al., “Phase I Study of Random Healthy Donor-Derived Allogeneic Natural Killer Cell Therapy in Patients with Malignant Lymphoma or Advanced Solid Tumors,” Cancer Immunology Research, Mar. 1, 2016, 4(3):215-224.
[cited by applicant]
AU Office Action in Australian Appln. No. 2018271755, dated Jun. 29, 2021, 3 pages.
[cited by applicant]
JP Office Action in Japanese Appln. No. 2019-565241, dated Jun. 22, 2021, 10 pages (with English translation).
[cited by applicant]
Li et al., “Expansion of NK cells from PBMCs using immobilized 4-1BBL and interleukin-21”, International Journal of Oncology, 2015, 47:335-342.
[cited by applicant]
U.S. Appl. No. 14/367,813, filed Jun. 20, 2014, Min et al.
[cited by applicant]
U.S. Appl. No. 15/527,752, filed May 18, 2017, Min et al.
[cited by applicant]
U.S. Appl. No. 16/702,978, filed Dec. 4, 2019, Min et al.
[cited by applicant]
U.S. Appl. No. 17/040,661, filed Jan. 14, 2021, Hwang et al.
[cited by applicant]
U.S. Appl. No. 17/220,865, filed Apr. 1, 2021, Min et al.
[cited by applicant]
U.S. Appl. No. 17/293,835, filed May 13, 2021, Kim et al.
[cited by applicant]
Carswell et al., “Culture of Human T Cells in Stirred Bioreactors for Cellular Immunotherapy Applications: Shear, Proliferation, and the IL-2 Receptor,” Biotechnology & Bioengineering, May 5, 2000, 68(3):328-338.
[cited by applicant]
Granzin et al., “'Fully automated expansion and activation of clinical-grade natural killer cells for adoptive immunotherapy,” Cytotherapy, May 2015, 17(5):621-632.
[cited by applicant]
Granzin et al., “Highly efficient IL-21 and feeder cell-driven ex vivo expansion of human NK cells with therapeutic activity in a xenograft mouse model of melanoma,” OncoImmunology, 2016, 5(9):e1219007.
[cited by applicant]
Granzin, “Highly Efficient Activation and Expansion of Natural Killer Cells For Clinical Use in Cancer Immunotherapy,” Dissertation for the Degree of Doctor of Natural Sciences, Combined Faculties for the Natural Scienc…
[cited by applicant]
Min et al., “Harnessing novel engineered feeder cells expressing activating molecules for optimal expansion of NK cells with potent antitumor activity,” Cellular & Molecular Immunology, 2022, 19(2):296-298 (Supplemental…
[cited by applicant]
Peirson et al., “Production of Human Natural Killer Cells for Adoptive Immunotherapy Using a Computer-Controlled Stirred-Tank Bioreactor, ” Journal of Hematotherapy, 1996, 5(5):475-483.
[cited by applicant]
Valle et al., “Heterogeneous CD3 Expression Levels in Differing T Cell Subsets Correlate with the In Vivo Anti-CD3-Mediated T Cell Modulation,” The Journal of Immunology, 2015, 194:2117-2127.
[cited by applicant]
CN Office Action in Chinese Application No. 201880034893.8, dated Feb. 11, 2023, 17 pages (with English Translation).
[cited by applicant]
GenBank Accession No. LN874322.1, “TPA_inf:
[cited by applicant]
U.S. Appl. No. 18/455,003, filed Aug. 24, 2023, Min et al.
[cited by applicant]
Cheng et al., “NK cell-based immunotherapy for malignant diseases,” Cell. Mol. Immunol., May 2013, 10(3):230-252.
[cited by applicant]
GenBank Accession No. NM_000594.3, “
[cited by applicant]
GenBank Accession No. NM_003811.3, “
[cited by applicant]
GenPept Accession No. NP_003317, “tumor necrosis factor ligand superfamily member 4 isoform 1 [
[cited by applicant]
GenPept Accession No. PDB:20QP_A, “Chain A, Interleukin-21,” May 17, 2018, 2 pages.
[cited by applicant]
Mock et al., “Automated manufacturing of chimeric antigen receptor T cells for adoptive immunology using CliniMACs Prodigy,” Cytotherapy, Aug. 2016, 18(8):1002-1011.
[cited by applicant]
Office Action in Canadian Application No. 3,062,130, dated Jan. 19, 2024, 4 pages.
[cited by applicant]