[미국특허]
Natural killer cells modified to express membrane-bound interleukin 15 and uses thereof
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/20
C12N-005/0783
A61K-035/17
C12N-005/00
C12N-015/62
C07K-014/54
C07K-014/705
출원번호
16550548
(2019-08-26)
등록번호
10774311
(2020-09-15)
발명자
/ 주소
Campana, Dario
Shook, David
Imamura, Masaru
출원인 / 주소
National University of Singapore
대리인 / 주소
Hamilton, Brook, Smith & Reynolds, P.C.
인용정보
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0인용 특허 :
0
초록▼
The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional por
The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and/or survival of NK cells.
대표청구항▼
1. A method of treating a cancer, the method comprising: administering to a subject having the cancer a population of Natural Killer (NK) cells that expresses all or a functional portion of interleukin-15 (IL-15), wherein the all or a functional portion of the IL-15 is fused to all or a portion of a
1. A method of treating a cancer, the method comprising: administering to a subject having the cancer a population of Natural Killer (NK) cells that expresses all or a functional portion of interleukin-15 (IL-15), wherein the all or a functional portion of the IL-15 is fused to all or a portion of a transmembrane protein that anchors the expressed IL-15 as a cell membrane-bound polypeptide (mbIL15) of the NK cell, and wherein the all or a functional portion of IL-15 promotes one or more of: (i) NK cell survival,(ii) regulation of NK cell and T cell activation and proliferation, and(iii) support of NK cell development from hematopoietic stem cells. 2. The method of claim 1, further comprising administering IL-2 to the individual. 3. The method of claim 1, further comprising administering one or more antibodies directed against the cancer to the individual. 4. The method of claim 1, wherein the transmembrane protein is selected from the group consisting of CD8α, CD4, CD3ε, CD3γ, CD3δ, CD3ζ, CD28, CD137, glycophorin A, glycophorin D, nicotinic acetylcholine receptor, a GABA receptor, FcεRIγ, and a T-cell receptor. 5. The method of claim 1, wherein the membrane-bound IL15 activates IL-15 signaling and/or anti-apoptotic signaling in an autocrine manner. 6. The method of claim 1, wherein the transmembrane protein comprises CD8α, wherein the mbIL15 comprises the amino acid sequence of SEQ ID NO: 4, and wherein the NK cells expressing all or a functional portion of IL-15 as a membrane-bound polypeptide exhibits enhanced expression of one or more activation receptors as compared to NK cells not expressing membrane-bound IL15, wherein the one or more activation receptors are selected from the group consisting of NKG2D, NKp44 (CD336) and NKp30 (CD337), CD16 and CD56. 7. The method of claim 1, wherein the cancer is selected from the group consisting of leukemia, a myelodysplastic syndrome, a lymphoma, a solid tumor, and a sarcoma. 8. The method of claim 7, wherein the cancer is a leukemia, and wherein the leukemia is acute lymphoblastic leukemia, acute myeloid leukemia, chronic myelogenous leukemia, or chronic lymphocytic leukemia. 9. The method of claim 7, wherein the cancer is a solid tumor, and wherein the solid tumor is a result of hepatocellular carcinoma, colon cancer, breast cancer, prostate cancer, gastric cancer, nasopharyngeal carcinoma, or neuroblastoma, high grade glioma.
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