JPWO2019152387A5 - - Google Patents
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- JPWO2019152387A5 JPWO2019152387A5 JP2020562093A JP2020562093A JPWO2019152387A5 JP WO2019152387 A5 JPWO2019152387 A5 JP WO2019152387A5 JP 2020562093 A JP2020562093 A JP 2020562093A JP 2020562093 A JP2020562093 A JP 2020562093A JP WO2019152387 A5 JPWO2019152387 A5 JP WO2019152387A5
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- JP
- Japan
- Prior art keywords
- cell
- cells
- pharmaceutical composition
- tgf
- tgfβi
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 210000000822 Killer Cells, Natural Anatomy 0.000 claims description 51
- 210000004693 NK cell Anatomy 0.000 claims description 34
- 210000004027 cells Anatomy 0.000 claims description 29
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 18
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 18
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N Tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 16
- 230000004913 activation Effects 0.000 claims description 8
- 238000000338 in vitro Methods 0.000 claims description 8
- 201000011510 cancer Diseases 0.000 claims description 7
- 102000004127 Cytokines Human genes 0.000 claims description 6
- 108090000695 Cytokines Proteins 0.000 claims description 6
- 230000002147 killing Effects 0.000 claims description 6
- 201000009910 diseases by infectious agent Diseases 0.000 claims description 5
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 claims description 4
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims description 4
- 102100016020 IFNG Human genes 0.000 claims description 4
- 101700086956 IFNG Proteins 0.000 claims description 4
- 206010024324 Leukaemias Diseases 0.000 claims description 4
- 102000004268 Smad3 Protein Human genes 0.000 claims description 4
- 108010042057 Smad3 Protein Proteins 0.000 claims description 4
- 102100008284 TGFBR3 Human genes 0.000 claims description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 4
- 108010001801 Tumor Necrosis Factor-alpha Proteins 0.000 claims description 4
- 108010079292 betaglycan Proteins 0.000 claims description 4
- 230000014509 gene expression Effects 0.000 claims description 4
- 206010005949 Bone cancer Diseases 0.000 claims description 2
- 241000282465 Canis Species 0.000 claims description 2
- 210000001808 Exosomes Anatomy 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 206010025310 Other lymphomas Diseases 0.000 claims description 2
- 208000001756 Virus Disease Diseases 0.000 claims description 2
- 201000005216 brain cancer Diseases 0.000 claims description 2
- 230000000139 costimulatory Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000002105 nanoparticle Substances 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 10
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
Description
本発明は、その好ましい態様に関して特に示し、かつ記載してきたが、形式および詳細の種々の変更が添付の特許請求の範囲によって包含される発明の範囲から逸脱することなくその中になされてもよいことが当業者によって理解されよう。前述の明細書において引用したすべての特許、刊行物および参考文献は、その全体が参照により本明細書に援用される。
本発明は、以下の態様を含み得る。
［１］
それを必要としている対象における癌または感染症を治療する方法であって、トランスフォーミング増殖因子β（TGF-β）スーパーファミリーインプリントされたナチュラルキラー（TGFβi NK）細胞の治療的に有効な数を前記対象に投与することを含む、方法。
［２］
前記対象が、感染症を有する、［１］に記載の方法。
［３］
前記感染症が、ウイルス感染症である、［２］に記載の方法。
［４］
前記対象が、癌を有する、［１］に記載の方法。
［５］
前記癌が、固形腫瘍である、［４］に記載の方法。
［６］
前記癌が、白血病、リンパ腫、横紋筋肉腫、脳癌および骨癌からなる群から選択される、［４］に記載の方法。
［７］
前記TGFβi NK細胞が、TGF-βに抵抗性である、［４］に記載の方法。
［８］
前記TGFβi NK細胞が、IFN-γ、TNF-αおよびGM-CSFの1つまたは複数の増加した量を産生する、［１］に記載の方法。
［９］
前記TGFβi NK細胞が、SMAD3タンパク質および／またはTGFBR3タンパク質の低減したレベルを示す、［１］に記載の方法。
［１０］
前記TGFβi NK細胞が、図12に示したものと実質的に類似の遺伝子発現プロファイルを有する、［１］に記載の方法。
［１１］
前記TGFβi NK細胞が、薬学的に許容される担体と共に投与される、［１］に記載の方法。
［１２］
TGF-βスーパーファミリーサイトカインに対して増加した抵抗性を示すナチュラルキラー（NK）細胞またはNK細胞株。
［１３］
前記NK細胞または細胞株が、TGF-βに対して増加した抵抗性を示す、［１２］に記載のNK細胞または細胞株。
［１４］
前記NK細胞が、増加した量のIFN-γ、TNF-αおよびGM-CSFのうちの1つまたは複数を産生する、［１２］に記載のNK細胞または細胞株。
［１５］
前記NK細胞が、SMAD3タンパク質および／またはTGFBR3タンパク質の低減したレベルを示す、［１２］に記載のNK細胞または細胞株。
［１６］
前記NK細胞が、図12に示したものと実質的に類似の遺伝子発現プロファイルを有する、［１２］に記載のNK細胞または細胞株。
［１７］
前記NK細胞が、TGF-βの存在下におけるナチュラルキラー細胞のインビトロ活性化によって調製される、［１２］に記載のNK細胞または細胞株。
［１８］
前記NK細胞が、ヒトNK細胞である、［１２］に記載のNK細胞または細胞株。
［１９］
前記NK細胞が、イヌNK細胞である、［１２］に記載のNK細胞または細胞株。
［２０］
TGF-βスーパーファミリーインプリントされたナチュラルキラー（TGFβi NK）細胞株を作製する方法であって、TGF-βスーパーファミリーサイトカインの存在下におけるナチュラルキラー細胞のインビトロ活性化を含む、方法。
［２１］
前記TGFβi NK細胞株が、TGF-βの存在下において活性化される、［２０］に記載の方法。
［２２］
白血病フィーダー細胞の存在下におけるナチュラルキラー細胞のインビトロ活性化をさらに含む、［２０］に記載の方法。
［２３］
前記フィーダー細胞が、K562フィーダー細胞である、［２２］に記載の方法。
［２４］
前記K562フィーダー細胞が、共刺激タンパク質および／またはサイトカインを発現するように遺伝的に修飾される、［２３］に記載の方法。
［２５］
NK刺激エキソソームまたはNK刺激ナノ粒子の存在下におけるナチュラルキラー細胞のインビトロ活性化をさらに含む、［２０］に記載の方法。
Although the present invention has been specifically shown and described with respect to its preferred embodiments, various modifications of form and detail may be made therein without departing from the scope of the invention covered by the appended claims. That will be understood by those skilled in the art. All patents, publications and references cited in the above specification are hereby incorporated by reference in their entirety.
The present invention may include the following aspects.
[1]
A method of treating cancer or infectious disease in subjects in need of it, a therapeutically effective number of transforming growth factor β (TGF-β) superfamily-imprinted natural killer (TGFβi NK) cells. A method comprising administering to said subject.
[2]
The method according to [1], wherein the subject has an infectious disease.
[3]
The method according to [2], wherein the infectious disease is a viral infectious disease.
[4]
The method according to [1], wherein the subject has cancer.
[5]
The method according to [4], wherein the cancer is a solid tumor.
[6]
The method according to [4], wherein the cancer is selected from the group consisting of leukemia, lymphoma, rhabdomyosarcoma, brain cancer and bone cancer.
[7]
The method according to [4], wherein the TGFβi NK cells are resistant to TGF-β.
[8]
The method according to [1], wherein the TGFβi NK cells produce an increased amount of one or more of IFN-γ, TNF-α and GM-CSF.
[9]
The method according to [1], wherein the TGFβi NK cells show reduced levels of SMAD3 protein and / or TGFBR3 protein.
[10]
The method according to [1], wherein the TGFβi NK cells have a gene expression profile substantially similar to that shown in FIG.
[11]
The method according to [1], wherein the TGFβi NK cells are administered together with a pharmaceutically acceptable carrier.
[12]
Natural killer (NK) cells or NK cell lines showing increased resistance to TGF-β superfamily cytokines.
[13]
The NK cell or cell line according to [12], wherein the NK cell or cell line exhibits increased resistance to TGF-β.
[14]
The NK cell or cell line according to [12], wherein the NK cell produces an increased amount of one or more of IFN-γ, TNF-α and GM-CSF.
[15]
NK cell or cell line according to [12], wherein the NK cell exhibits reduced levels of SMAD3 protein and / or TGFBR3 protein.
[16]
The NK cell or cell line according to [12], wherein the NK cell has a gene expression profile substantially similar to that shown in FIG.
[17]
The NK cell or cell line according to [12], wherein the NK cell is prepared by in vitro activation of a natural killer cell in the presence of TGF-β.
[18]
The NK cell or cell line according to [12], wherein the NK cell is a human NK cell.
[19]
The NK cell or cell line according to [12], wherein the NK cell is a canine NK cell.
[20]
A method of making a TGF-β superfamily imprinted natural killer (TGFβi NK) cell line, comprising in vitro activation of natural killer cells in the presence of TGF-β superfamily cytokines.
[21]
The method according to [20], wherein the TGFβi NK cell line is activated in the presence of TGF-β.
[22]
The method according to [20], further comprising in vitro activation of natural killer cells in the presence of leukemia feeder cells.
[23]
The method according to [22], wherein the feeder cell is a K562 feeder cell.
[24]
23. The method of [23], wherein the K562 feeder cells are genetically modified to express costimulatory proteins and / or cytokines.
[25]
The method according to [20], further comprising in vitro activation of natural killer cells in the presence of NK-stimulated exosomes or NK-stimulated nanoparticles.
Claims (22)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862623682P | 2018-01-30 | 2018-01-30 | |
| US62/623,682 | 2018-01-30 | ||
| PCT/US2019/015617 WO2019152387A1 (en) | 2018-01-30 | 2019-01-29 | Transforming growth factor beta-resistant natural killer cells |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2021512164A JP2021512164A (en) | 2021-05-13 |
| JPWO2019152387A5 true JPWO2019152387A5 (en) | 2022-01-27 |
Family
ID=67478491
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020562093A Pending JP2021512164A (en) | 2018-01-30 | 2019-01-29 | Transforming Growth Factor Beta Resistant Natural Killer Cells |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20200368281A1 (en) |
| EP (1) | EP3746118A4 (en) |
| JP (1) | JP2021512164A (en) |
| KR (1) | KR20200118449A (en) |
| CN (1) | CN111818941A (en) |
| AU (1) | AU2019213678A1 (en) |
| BR (1) | BR112020015490A2 (en) |
| CA (1) | CA3090096A1 (en) |
| IL (2) | IL276374B2 (en) |
| MX (1) | MX2020008044A (en) |
| RU (1) | RU2020127722A (en) |
| SG (1) | SG11202007288VA (en) |
| WO (1) | WO2019152387A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20230181637A1 (en) * | 2020-03-11 | 2023-06-15 | Research Institute At Nationwide Children's Hospital | Nk cells and uses thereof for treatment of microbial infections |
| EP4142752A4 (en) * | 2020-04-30 | 2024-08-07 | Res Inst Nationwide Childrens Hospital | Overcoming immune suppression with tgf-beta resistant nk cells |
| WO2024182801A1 (en) * | 2023-03-02 | 2024-09-06 | Research Institute At Nationwide Children's Hospital | Transforming growth factor-beta superfamily-imprinted natural killer cells for cancer immunotherapy |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2058388A1 (en) * | 2007-10-05 | 2009-05-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Non-conventional NKT cells for use in cancer therapy |
| US9796960B2 (en) * | 2014-01-13 | 2017-10-24 | Mingjie Zhang | Method for preparing and using cell ghost with active factors as synergist of lymphocyte in vitro culture |
| WO2016069607A1 (en) * | 2014-10-27 | 2016-05-06 | University Of Central Florida Research Foundation, Inc. | Methods and compositions for natural killer cells |
| KR20180040706A (en) * | 2015-09-01 | 2018-04-20 | 인네이트 튜머 이뮤니티, 인코포레이티드 | Immune cells having increased immunity or resistance to immunosuppressive cytokines and uses thereof |
| US10995317B2 (en) * | 2015-09-14 | 2021-05-04 | Regents Of The University Of Minnesota | NK cells exhibiting an adaptive phenotype and methods for preparing and for using |
-
2019
- 2019-01-29 KR KR1020207024676A patent/KR20200118449A/en not_active Application Discontinuation
- 2019-01-29 SG SG11202007288VA patent/SG11202007288VA/en unknown
- 2019-01-29 BR BR112020015490-3A patent/BR112020015490A2/en unknown
- 2019-01-29 US US16/966,367 patent/US20200368281A1/en active Pending
- 2019-01-29 IL IL276374A patent/IL276374B2/en unknown
- 2019-01-29 AU AU2019213678A patent/AU2019213678A1/en active Pending
- 2019-01-29 RU RU2020127722A patent/RU2020127722A/en unknown
- 2019-01-29 JP JP2020562093A patent/JP2021512164A/en active Pending
- 2019-01-29 CN CN201980016864.3A patent/CN111818941A/en active Pending
- 2019-01-29 IL IL309656A patent/IL309656A/en unknown
- 2019-01-29 EP EP19747119.6A patent/EP3746118A4/en active Pending
- 2019-01-29 CA CA3090096A patent/CA3090096A1/en active Pending
- 2019-01-29 MX MX2020008044A patent/MX2020008044A/en unknown
- 2019-01-29 WO PCT/US2019/015617 patent/WO2019152387A1/en unknown
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