JP2020506183A - 造血幹細胞移植を受けている患者を治療するための便細菌叢 - Google Patents
造血幹細胞移植を受けている患者を治療するための便細菌叢 Download PDFInfo
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- JP2020506183A JP2020506183A JP2019540408A JP2019540408A JP2020506183A JP 2020506183 A JP2020506183 A JP 2020506183A JP 2019540408 A JP2019540408 A JP 2019540408A JP 2019540408 A JP2019540408 A JP 2019540408A JP 2020506183 A JP2020506183 A JP 2020506183A
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Abstract
Description
- 自己移植、これは、患者が、骨髄、又は数週間、数か月又は数年前に末梢血から採取した自分自身の幹細胞を受領し、凍結保存する。
- 同種移植、(又は「同種異系移植(allogenic graft)」)、これは、適合性の有無にかかわらず、関連するドナー、又は適合性の有無にかかわらず、無関係のドナー、又は臍帯血細胞が必要である。
この治療上の必要性に応えて、本発明者達は、HSC移植と便細菌叢移植とを組み合わせることを提案する。本発明者達は、便細菌叢ドナーが、HSCドナーと同じである場合の利点をより具体的に特定した。発明者達はまた、同種の状態の場合であっても(便細菌叢ドナーとHSCドナーが同一の場合)、便細菌叢ドナーとHSCドナーが異なる状態であろうと、HSC移植前の便細菌叢移植の利点を確認した。
受領患者
想定される患者は、年齢及び性別にかかわらず、造血幹細胞移植を受けた、又は受ける予定のあるヒトである。患者は、HSC移植によって治療することができる何れかの障害を患っている。これらは、特に癌、遺伝的障害、造血系及び/又は免疫系に影響を及ぼす障害である。特に、慢性骨髄性白血病、急性骨髄性白血病、急性リンパ性白血病、骨髄増殖性症候群、骨髄異形成症候群、NHL(非ホジキン悪性リンパ腫)、ホジキン病、多発性骨髄腫、特発性髄質形成不全、発作性寒冷ヘモグロビン尿症、ヘモグロビン症、先天性免疫不全(SCID、Kostmann、Wiskott−Aldrich)及びファンコニー貧血を含む固形腫瘍、悪性血液疾患が言及され得る。
本発明は、特定の実施形態において、HSCドナー対象と同じドナー対象から有利に生じ得る便細菌叢移植を実施する。
i)ドナー対象からの便サンプルを抗凍結剤及び/又は充填剤を含む生理食塩水性溶液と混合することにより解凍すること、
ii)任意に、その後、濾過すること、
iii)貯蔵のために凍結する前に、混合及び凍結の工程が、好ましくは嫌気性条件下で行われること、
によって得られ得る本発明において用いられる。
a)ドナー対象から少なくとも1つの便細菌叢サンプルを採取する工程、
b)a)で得られた前記サンプルを、好ましくはサンプル採取後5分以内の制限時間内に、好ましくは酸素に対して密閉された収集装置に入れる工程、
c)b)で得られたサンプルを、少なくとも1つの抗凍結剤及び/又は充填剤を含む少なくとも1つの生理食塩水性溶液と混合する工程、
d)任意に、特に、0.7mm以下、好ましくは、0.5mm以下の直径の細孔を含むフィルターにより、c)で得られた混合物を濾過する工程、及び
e)典型的に、−15℃〜−100℃、好ましくは−60℃〜−90℃の温度で凍結することにより、c)又はd)で得られた混合物を貯蔵する工程、
工程b)〜e)は、好ましくは、嫌気的に行われる。
- 塩化ナトリウム、塩化カルシウム、塩化マグネシウム、塩化カリウム、グルコン酸ナトリウム、酢酸ナトリウムから選択される少なくとも1つの塩、及び
- 任意に、好ましくは、L−アスコルビン酸ナトリウム、トコフェロール類、L−システイン塩酸塩一水和物及びそれらの混合物から選択される少なくとも1つの酸化防止剤。
- 上記の少なくとも1つの抗凍結剤、すなわち、ポリオール、二糖〜五糖(すなわち、二糖、三糖、四糖及び五糖)、DMSO及びそれらの混合物から選択される、及び
- 上記の少なくとも1つの充填剤、すなわち、デンプン又は排泄物の部分加水分解物から選択される充填剤、好ましくは、充填剤は、マルトデキストリンによって構成される。
受領患者における同種異系HSC移植(HSC)に起因する感染性又は非感染性合併症の予防及び/又は治療方法は、本明細書に記載されており、便細菌叢のサンプルの前記受領患者への投与を含み、前記便細菌叢のサンプル及び前記造血幹細胞は、好ましくはドナー対象に由来する。「同種異系HSC移植に起因する感染性又は非感染性合併症」とは、特に、同種異系HSC移植に対する患者の前処理、患者の免疫防御を低下させる前処理による合併症、並びに同種異系移植事体による合併症、すなわち、特に急性及び/又は慢性形態の移植対宿主(GVH)疾患を意味する。
便細菌叢のサンプルは、前記HSC移植の前又は後に受領患者の消化管に投与され得る(用語「移植された」も用いられる)。
患者は、急性骨髄性白血病に罹患した16歳の少女で、最初のHSC同種移植後に再発した。
胃腸の症状は著しく減少し、検査は、クロストリジウム・ディフィシル感染からの回復及びバンコマイシン耐性エンテロコッカスの根絶を示した。
Claims (14)
- 受領患者における同種異系造血幹細胞(HSC)移植に起因する感染性又は非感染性合併症の予防及び/又は治療に使用するための便細菌叢のサンプルであって、前記便細菌叢のサンプルが、HSC移植前に投与される、サンプル。
- 前記サンプルが、便細菌叢であり、前記造血幹細胞が、同一のドナー対象に由来する、請求項1に記載の使用のための便細菌叢のサンプル。
- 受領患者における同種異系造血幹細胞(HSC)移植に起因する感染性又は非感染性合併症の予防及び/又は治療に使用するための便細菌叢のサンプルであって、前記便細菌叢のサンプル及び前記造血幹細胞が、同一ドナー対象に由来する、サンプル。
- 前記HSC移植後に受領患者の消化管にサンプルを移植することが、好ましくは、前記HSC移植の1週間〜2年後に受領患者の消化管にサンプルを移植することが、必要に応じて繰り返される、請求項3に記載の使用のための便細菌叢のサンプル。
- 前記HSC移植の前に受領患者の消化管にサンプルを移植すること、前記HSC移植の1週間〜12か月、好ましくは1週間〜8か月、好ましくは1週間〜6か月、より好ましくは1週間〜4か月、好ましくは1週間〜3か月、又は1〜8週間前に受領患者の消化管にサンプルを移植することが、必要に応じて繰り返される、請求項1〜3の何れか1項に記載の使用のための便細菌叢のサンプル。
- クロストリジウム(Clostridium)又はエンテロコッカス(Enterococci)による感染、特にバンコマイシン耐性エンテロコッカス(enterococci)(VRE)による感染の予防及び/又は治療における、請求項1〜5の何れか1項に記載の使用のための便細菌叢のサンプル。
- GVH疾患の予防及び/又は治療における、請求項1〜6の何れか1項に記載の使用のための便細菌叢のサンプル。
- 受領患者が、癌に罹患している、請求項1〜7の何れか1項に記載の使用のための便細菌叢のサンプル。
- 癌に罹患しており同種異系造血幹細胞移植を受けている又は受けた受領患者の癌の治療に使用するための便細菌叢のサンプルであって、前記便細菌叢のサンプル及び前記造血幹細胞が、同一ドナー対象に由来する、サンプル。
- 前記HSC移植の前に受領患者の消化管にサンプルを移植すること、前記HSC移植の1週間〜12か月、好ましくは1週間〜8か月、好ましくは1週間〜6か月、より好ましくは1週間〜4か月、好ましくは1週間〜3か月、又は1〜8週間前に受領患者の消化管にサンプルを移植することが、必要に応じて繰り返される、請求項9に記載の便細菌叢のサンプル。
- 前記HSC移植の後に受領患者の消化管にサンプルを移植すること、好ましくは、前記HSC移植の1週間〜2年後に受領患者の消化管にサンプルを移植することが、必要に応じて繰り返される、請求項9に記載の便細菌叢のサンプル。
- 前記受領患者が、悪性血液疾患に罹患している、1〜11の何れか1項に記載の便細菌叢のサンプル。
- 前記サンプルが、
i)ドナー対象からの便サンプルを抗凍結剤及び/又は充填剤を含む生理食塩水性溶液と混合することにより解凍すること、
ii)任意に、その後、濾過すること、
iii)貯蔵のために凍結する前に、混合及び凍結の工程が、好ましくは嫌気性条件下で行われること、
によって得られる、請求項1〜12の何れか1項に記載の便細菌叢のサンプル。 - 直腸経路を介した投与による、請求項1〜13の何れか1項に記載の使用のための便細菌叢のサンプル。
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FR1750629 | 2017-01-26 | ||
PCT/EP2018/051941 WO2018138251A1 (fr) | 2017-01-26 | 2018-01-26 | Microbiote fecal pour traiter des patients subissant une greffe de cellules souches hematopoietiques |
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PL3573631T3 (pl) | 2023-05-02 |
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WO2018138251A1 (fr) | 2018-08-02 |
IL268237A (en) | 2019-09-26 |
EP3573631B1 (fr) | 2022-11-16 |
DK3573631T3 (da) | 2023-01-30 |
IL268237B (en) | 2022-07-01 |
HUE061155T2 (hu) | 2023-05-28 |
FR3062063A1 (fr) | 2018-07-27 |
AU2018212530B2 (en) | 2022-06-23 |
KR20190130563A (ko) | 2019-11-22 |
CN110520141A (zh) | 2019-11-29 |
PT3573631T (pt) | 2023-01-24 |
ES2937965T3 (es) | 2023-04-03 |
RS63978B1 (sr) | 2023-03-31 |
KR102517287B1 (ko) | 2023-03-31 |
SI3573631T1 (sl) | 2023-09-29 |
FI3573631T3 (fi) | 2023-03-02 |
FR3062063B1 (fr) | 2019-04-19 |
CA3051807A1 (fr) | 2018-08-02 |
EP3573631A1 (fr) | 2019-12-04 |
AU2018212530A1 (en) | 2019-09-05 |
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US20200188450A1 (en) | 2020-06-18 |
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