JP2016535009A - 抗体依存性エキソソーム治療の方法 - Google Patents
抗体依存性エキソソーム治療の方法 Download PDFInfo
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Abstract
Description
本発明は、国立癌研究所により授与された助成金番号CA081403−14の元で、及び国立衛生研究所により授与された助成金番号047599−09の元で、政府の支援を受けてなされた。政府は、本発明に対し一定の権利を有する。
抗体依存性エキソソーム治療(ADET)のためエキソソームを含む組成物を用いて、がんを治療するための組成物及び方法が本明細書に記載されている。
Fc受容体を含むエキソソームと薬学的に許容可能な担体とを含む薬学的組成物が、本明細書に提供される。組成物は、天然にFc受容体を発現する細胞、またはFc受容体を発現するように遺伝子操作された細胞由来のエキソソームを含む。Fc受容体は、FcγR1(CD64)、FcγR2(CD32)、FcγR3(CD16)またはその組み合わせの1つ若しくはそれ以上であり得る。Fc受容体を天然に発現する細胞の例としては、活性化ナチュラルキラー(aNK)細胞が挙げられるが、それに限定されない。Fc受容体を発現するように遺伝的に操作し得る細胞の例としては、T細胞、マクロファージ、幹細胞、間葉系幹細胞、またはその組み合わせが挙げられるがそれに限定されない。Fc受容体を含むエキソソームを含有する組成物は、抗体、タンパク質、ペプチド、核酸、小分子薬、またはその組み合わせを含むがそれに限定されない治療剤を含有する。一態様において、エキソソームは、Fc受容体、及びFc受容体を介してエキソソームを標的細胞(がん細胞など)に対して向ける1つ若しくはそれ以上の抗体を含有する。幾つかの態様において、エキソソームは、Fc受容体、1つ若しくはそれ以上の抗体及び1つ若しくはそれ以上の追加の治療剤を含む。治療剤は、化学治療剤、免疫調節剤、抗菌剤、抗ウイルス剤、抗寄生虫剤またはその組み合わせを含むことができる。
また、本明細書において、がんを処置し、がんを阻害し、がんの転移を予防し、がんの重症度を低下させ、がんの寛解を促進し、及び/または、それを必要とする対象におけるがんの再発の可能性を予防し、または低減するための方法が提供される。方法は、細胞から単離されたFc受容体を含有するエキソソームを含む組成物を提供する段階、並びにがんを処置し、がんを阻害し、がんの転移を予防し、がんの重症度を低下させ、がんの寛解を促進し、及び/または、対象におけるがんの再発の可能性を予防し、低減するために、対象に有効量の組成物を投与する段階を含む。様々な態様において、エキソソームは、天然のまま、または本明細書に記載するように操作することができる。幾つかの態様において、エキソソームは、FcγR1(CD64)、FcγR2(CD32)、FcγR3(CD16)、またはその組み合わせのいずれか1つまたはそれ以上を含むFc受容体を含有する。一態様において、エキソソームは、FcγR1(CD64)、FcγR3(CD16)、またはそれらの組み合わせを含む、Fc受容体を含有する。一態様において、エキソソームは、FcγR1(CD64)を含む。様々な態様において、エキソソーム(天然または操作された)は、抗体、脂質、ペプチド、タンパク質、核酸、小分子、またはその組み合わせを含むがそれに限定されない治療剤を含有する。幾つかの態様において、本明細書に記載の組成物は、追加の治療剤と共に投与される。幾つかの態様において、エキソソームは、エキソソームをがん細胞に対して向けるように、抗体が負荷される。幾つかの態様において、抗体は、同時に、または順次に、エキソソームと共に投与される。更なる態様において、エキソソームは、追加の治療剤(例えば、化学治療剤など)と共に投与される。エキソソームと一緒に投与される治療剤は、エキソソームを含む組成物の投与の前、投与中、投与後に投与することができる。
本発明は、また、がんを処置し、がんの転移を予防し、がんの重症度を低下させ、がんの寛解を促進し、及び/または、それを必要とする対象におけるがんの再発の可能性を予防し、減少させるためのキットを提供する。キットは、本明細書に記載の薬学的組成物と、がんを処置し、がんを予防し、がんの重症度を低下させ、がんの寛解を促進し、及び/または、それを必要とする対象におけるがんの再発の可能性を予防し、または減少させるための組成物の使用のための指示書とを含む。幾つかの態様において、がんは神経芽腫である。幾つかの態様において、がんは、ALLまたは他の白血病のサブタイプである。キットは、本明細書に記載の組成物のうちの少なくとも1つを含む、材料または構成要素の組み合わせである。
また、本明細書中において、標的細胞、及び/または、組織へのエキソソームの標的化効力を決定することを含む抗体依存エキソソーム治療の有効性を決定する方法を提供する。幾つかの態様において、標的細胞、及び/または、組織へのエキソソームの標的有効性を決定することは、標的細胞、及び/または、組織中で、エキソソームに特異的な核酸、及び/または、タンパク質を検出することを含む。標的細胞、及び/または、組織中のエキソソーム特異的核酸、及び/または、タンパク質の存在は、有効な抗体依存性エキソソーム治療の指標である。幾つかの態様において、エキソソームは、活性化ナチュラルキラー細胞に由来する。幾つかの態様において、エキソソームは、エキソソーム特異的タンパク質、及び/または、エキソソームに固有の核酸を含むように操作される。幾つかの態様において、核酸は、miRNA、mRNA、またはその組み合わせを含む。例示的な態様において、miRNAは、表4に記載されたmiRNAのいずれか1つ若しくはそれ以上であってもよい。更なる例示的な態様では、mRNAは、表5に記載されたmRNAのいずれか1つ若しくはそれ以上であってもよい。
Claims (27)
- Fc受容体を含むエキソソームと薬学的に許容可能な担体とを含む、薬学的組成物。
- 前記Fc受容体が、FcγR1(CD64)、FcγR2(CD32)、FcγR3(CD16)、またはその組み合わせのいずれか1つまたはそれ以上である、請求項1に記載の薬学的組成物。
- 前記エキソソームが、天然エキソソームである、請求項1に記載の薬学的組成物。
- 前記エキソソームが、活性化ナチュラルキラー細胞由来である、請求項3に記載の薬学的組成物。
- 前記エキソソームが、操作されたエキソソームである、請求項1に記載の薬学的組成物。
- 前記操作されたエキソソームが、FcγR1(CD64)、FcγR2(CD32)、FcγR3(CD16)、またはその組み合わせを含む、請求項5に記載の薬学的組成物。
- 前記エキソソームをがん細胞に対して向ける1つ若しくはそれ以上の抗体を更に含む、請求項1に記載の薬学的組成物。
- 1つ若しくはそれ以上の治療剤を更に含む、請求項15に記載の薬学的組成物。
- 前記治療剤が、脂質、ペプチド、タンパク質、抗体、小分子、オリゴヌクレオチド、核酸、またはその組み合わせのいずれか1つまたはそれ以上である、請求項17に記載の薬学的組成物。
- 細胞由来のエキソソームを含む組成物を提供する段階であって、該エキソソームがFc受容体を含む、段階;及び
対象のがんを処置するために、前記組成物の有効量を対象に投与する段階
を含む、それを必要とする対象のがんを処置する方法。 - 前記がんが、リンパ腫、肉腫、脳腫瘍、乳癌、結腸癌、肺癌、肝細胞癌、胃癌、膵臓癌、子宮頸癌、卵巣癌、肝臓癌、膀胱癌、尿路の癌、甲状腺癌、腎臓癌、癌腫、黒色腫、頭頸部癌、脳腫瘍、及び前立腺癌のいずれか1つまたはそれ以上である、請求項10に記載の方法。
- 前記がんが、神経芽腫または白血病である、請求項11に記載の方法。
- 前記白血病がALLである、請求項12に記載の方法。
- 前記組成物が、Fc受容体を産生する細胞から得られる天然エキソソームを含む、請求項10に記載の方法。
- 前記組成物が、Fc受容体を産生するように操作された細胞から得られる操作されたエキソソームを含む、請求項10に記載の方法。
- Fc受容体が、FcγR1(CD64)、FcγR2(CD32)、FcγR3(CD16)またはその組み合わせのいずれか1つまたはそれ以上である、請求項14または15に記載の方法。
- 前記細胞が、活性化ナチュラルキラー(aNK)細胞、T細胞、マクロファージ、幹細胞、間葉系間質細胞、またはその組み合わせのいずれか1つまたはそれ以上である、請求項14または15に記載の方法。
- 前記組成物が、1つ若しくはそれ以上の抗体を更に含み、該抗体が、エキソソームをがん細胞に対して向ける、請求項10に記載の方法。
- 前記抗体が、神経芽腫細胞の表面上の、GD2、CD24、CD25またはその組み合わせのいずれか1つまたはそれ以上を標的とする、請求項18に記載の方法。
- 前記抗体が、CD2、CD10、CD15、CD19、CD21、CD22、またはその組み合わせのいずれか1つまたはそれ以上を標的にする、請求項18に記載の方法。
- 前記組成物が、1つ若しくはそれ以上の治療剤を更に含む、請求項10に記載の方法。
- 前記治療剤が、脂質、ペプチド、タンパク質、抗体、小分子、オリゴヌクレオチド、核酸、またはその組み合わせのいずれか1つまたはそれ以上である、請求項19に記載の方法。
- 前記治療剤が、抗GD2抗体、3F8抗体、組換えGM−CSFまたはその変異体、イリノテカン/SN38、エトポシド、ドキソルビシン、フェンレチニド、PI−103、シクロホスファミド、またはその組み合わせのいずれか1つまたはそれ以上である、請求項22に記載の方法。
- Fc受容体を含むエキソソームと薬学的に許容可能な担体とを含む組成物;及び
がんの処置のための該組成物の使用のための指示書
を含む、キット。 - 前記組成物が、1つ若しくはそれ以上の抗体を更に含み、該抗体が、エキソソームをがん細胞に対して向ける、請求項24に記載のキット。
- 前記組成物が、1つ若しくはそれ以上の治療剤を更に含む、請求項24に記載のキット。
- 前記治療剤が、脂質、ペプチド、タンパク質、抗体、小分子、オリゴヌクレオチド、核酸、またはその組み合わせのいずれか1つまたはそれ以上である、請求項26に記載のキット。
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US201361892352P | 2013-10-17 | 2013-10-17 | |
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US62/038,734 | 2014-08-18 | ||
PCT/US2014/061245 WO2015058148A1 (en) | 2013-10-17 | 2014-10-17 | Antibody dependent exosome therapy |
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JP2016535009A true JP2016535009A (ja) | 2016-11-10 |
JP2016535009A5 JP2016535009A5 (ja) | 2017-11-09 |
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JP2016524060A Pending JP2016535009A (ja) | 2013-10-17 | 2014-10-17 | 抗体依存性エキソソーム治療の方法 |
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US (1) | US20160243192A1 (ja) |
EP (1) | EP3057662A4 (ja) |
JP (1) | JP2016535009A (ja) |
WO (1) | WO2015058148A1 (ja) |
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US20120315324A1 (en) | 2010-02-05 | 2012-12-13 | University Of Louisville Research Foundation, Inc. | Exosomal compositions and methods for the treatment of disease |
WO2013070324A1 (en) | 2011-11-07 | 2013-05-16 | University Of Louisville Research Foundation, Inc. | Edible plant-derived microvesicle compositions for diagnosis and treatment of disease |
CA3029602A1 (en) * | 2015-07-02 | 2017-01-05 | University Of Louisville Research Foundation, Inc. | Edible plant-derived microvesicle compositions for delivery of mirna and methods for treatment of cancer |
CA3004450A1 (en) | 2015-11-18 | 2017-05-26 | University Of Georgia Research Foundation, Inc. | Neural cell extracellular vesicles |
GB2552473A (en) * | 2016-07-21 | 2018-01-31 | Evox Therapeutics Ltd | Surface decoration of extracellular vesicles |
US10815520B2 (en) | 2017-04-07 | 2020-10-27 | University Of Louisville Research Foundation, Inc. | Nanovesicles, methods, and systems for diagnosis and prognosis of cancer |
EP3438250B1 (en) * | 2017-07-31 | 2022-12-07 | Rheinische Friedrich-Wilhelms-Universität Bonn | Cell derived extracellular vesicles for the treatment of diseases |
CN110669764B (zh) * | 2017-12-11 | 2020-12-11 | 浙江大学 | 一种hsa-miR-10367 miRNA序列在抗肿瘤中的应用 |
BR112020016228A2 (pt) * | 2018-02-12 | 2020-12-08 | Codiak Biosciences, Inc. | Métodos e composições para polarização de macrófagos |
US11607428B2 (en) | 2019-06-06 | 2023-03-21 | Spiritus Therapeutics, Inc. | Mesenchymal stem cell-derived extracellular vesicles and uses thereof for treating and diagnosing fibrotic diseases |
WO2020247675A1 (en) * | 2019-06-06 | 2020-12-10 | Spiritus Therapeutics, Inc. | Methods for attenuating viral infection and for treating lung injury |
US20210130782A1 (en) * | 2019-10-28 | 2021-05-06 | Augusta University Research Institute, Inc. | Engineered Exosomes to Detect and Deplete Pro-Tumorigenic Macrophages |
CN111450249A (zh) * | 2020-03-09 | 2020-07-28 | 杨静悦 | miRNA-320a的表达促进物在制备抑制肿瘤细胞药物中的应用 |
WO2022149779A1 (ko) * | 2021-01-11 | 2022-07-14 | 주식회사 엑소코바이오 | 과발현된 Fc 수용체 또는 이의 일부를 포함하는 엑소좀 및 이의 제조방법 |
WO2022158836A1 (ko) * | 2021-01-21 | 2022-07-28 | 주식회사 엑소코바이오 | 목적 단백질 또는 펩타이드가 융합가능한 Fc 수용체 또는 이의 일부를 포함하는 재조합 엑소좀 및 이의 용도 |
WO2023081109A1 (en) * | 2021-11-05 | 2023-05-11 | Malcolm Thomas | Tailored hypoimmune nanovesicular delivery systems for cancer tumors, hereditary and infectious diseases |
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JP4662708B2 (ja) * | 2001-08-17 | 2011-03-30 | エクソセラ・エルエルシー | エクソゾームにタンパク質を標的化する方法および組成物 |
US8795672B2 (en) * | 2003-02-14 | 2014-08-05 | University Of Southern California | Compositions and methods for cancer immunotherapy |
IL161899A0 (en) * | 2004-05-10 | 2005-11-20 | Hoffman Arnold | Kit for treatment of cancer |
KR101571027B1 (ko) * | 2006-06-12 | 2015-11-23 | 이머전트 프로덕트 디벨롭먼트 시애틀, 엘엘씨 | 효과기 기능을 갖는 단일쇄 다가 결합 단백질 |
US20120315324A1 (en) * | 2010-02-05 | 2012-12-13 | University Of Louisville Research Foundation, Inc. | Exosomal compositions and methods for the treatment of disease |
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- 2014-10-17 JP JP2016524060A patent/JP2016535009A/ja active Pending
- 2014-10-17 US US15/029,395 patent/US20160243192A1/en not_active Abandoned
- 2014-10-17 WO PCT/US2014/061245 patent/WO2015058148A1/en active Application Filing
Non-Patent Citations (3)
Title |
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CLIN. CANCER RES, vol. 19, no. 8, JPN6018021559, 15 April 2013 (2013-04-15), pages 2132 - 2143 * |
ONCOIMMUNOLOGY, vol. 2, no. 1, JPN6018021560, 1 January 2013 (2013-01-01), pages e22337 3pages * |
THE JOURNAL OF IMMUNOLOGY, vol. Vol.189, JPN6018021558, 2012, pages 2833 - 2842 * |
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EP3057662A4 (en) | 2017-03-29 |
US20160243192A1 (en) | 2016-08-25 |
EP3057662A1 (en) | 2016-08-24 |
WO2015058148A1 (en) | 2015-04-23 |
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