Granted Patent
B2
US 12,398,372 · App. 17/293,835 · Granted Aug 26, 2025
Method for culturing cord blood-derived natural killer cells using transformed T-cells
Inventors:
Yusun Kim (Yongin-si, KR); Eun Ji Kim (Yongin-si, KR); Gyeong-Min Park (Yongin-si, KR); Bitna Yang (Yongin-si, KR); Bokyung Min (Yongin-si, KR); Sungyoo Cho (Yongin-si, KR); Yu Kyeong Hwang (Yongin-si, KR)
Assignee:
GC Cell Corporation
C12N5/0646A61K40/15A61K40/42A61K2239/31A61K2239/38A61K2239/48C12N2501/2302C12N2501/515C12N2502/1114C12N2510/00
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Abstract
The present invention relates to a method for culturing cord blood-derived natural killer cells using transformed T cells. The method of the present invention uses transformed T cells to culture natural killer cells and enables effective proliferation and production of natural killer cells from a small amount of seed cells. In addition, natural killer cells produced by the method of the present invention have improved cytotoxicity. Therefore, the method of the present invention is useful in commercializing natural killer cells for cell therapy. Furthermore, natural killer cells produced by the method of the present invention are useful for cell therapy.
Claims (14)
1. A method for expanding natural killer cells, the method comprising:
co-culturing seed cells comprising cord blood-derived natural killer cells with a first population of feeder cells, wherein the first population of feeder cells comprises genetically engineered CD4+ T cells expressing a 4-1BBL polypeptide, a membrane-bound IL-21 polypeptide, and a TNF-α polypeptide comprising a mutated Tumor Necrosis Factor-α Converting Enzyme (TACE) recognition site, wherein the seed cells and genetically engineered CD4+ T cells are co-cultured in a medium comprising: 1,000 ng/ml of an anti-CD3 antibody; and IL-2, thereby expanding the natural killer cells;
wherein the seed cells comprise mononuclear cells derived from cord blood; and
wherein the seed cells are depleted of CD3(+) cells.
2. The method of claim 1 , wherein the genetically engineered CD4+ T cells are cells from a cell line selected from the group consisting of Jurkat, Peer, H9 and HuT78.
3. The method of claim 2 , wherein the genetically engineered CD4+ T cells are cells from a HuT78 cell line.
4. The method of claim 1 , wherein the 4-1BBL polypeptide comprises an amino acid sequence of SEQ ID NO: 1.
5. The method of claim 1 , wherein the membrane-bound IL-21 polypeptide comprises an amino acid sequence of SEQ ID NO: 3.
6. The method of claim 1 , wherein the TNF-α polypeptide comprises an amino acid sequence of SEQ ID NO: 8.
7. The method of claim 1 , wherein the method comprises mixing the genetically engineered CD4+ T cells and the seed cells at a ratio of between 0.1:1 and 50:1.
8. The method of claim 1 , wherein the method comprises co-culturing the genetically engineered CD4+ T cells and the seed cells for 5-60 days.
9. The method of claim 8 , wherein the method comprises co-culturing the genetically engineered CD4+ T cells and the seed cells for 14-21 days.
10. The method of claim 1 , wherein the method further comprises co-culturing the seed cells with a second population of feeder cells.
11. The method of claim 1 , wherein the 4-1BBL polypeptide comprises an amino acid sequence of SEQ ID NO: 1, the membrane-bound IL-21 polypeptide comprises an amino acid sequence of SEQ ID NO: 3, and the TNF-a polypeptide comprises an amino acid sequence of SEQ ID NO: 8.
Assignments (3)
CORRECTIVE ASSIGNMENT TO CORRECT THE THE FIRST INVENTORS NAME PREVIOUSLY RECORDED AT REEL: 056492 FRAME: 0288. ASSIGNOR(S) HEREBY CONFIRMS THE ASSUGNMENT.
Recorded Mar 23, 2022
From: KIM, YUSUN; KIM, EUN JI; PARK, GYEONG MIN; YANG, BITNA; MIN, BOKYUNG; CHO, SUNGYOO; HWANG, YU KYEONG
To: GREEN CROSS LAB CELL CORPORATION
Reel/Frame 059484/0886 →
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 Jun 9, 2021
From: KIM, YOU-SUN; KIM, EUN JI; PARK, GYEONG MIN; YANG, BITNA; MIN, BOKYUNG; CHO, SUNGYOO; HWANG, YU KYEONG
To: GREEN CROSS LAB CELL CORPORATION
Reel/Frame 056492/0288 →
Priority Claims (2)
KR 10-2018-0139722
· Nov 14, 2018
· national
KR 10-2019-0145068
· Nov 13, 2019
· national
Continuity (1)
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