JP2009526784A - 造血幹細胞の生着を増強するための方法および組成物 - Google Patents
造血幹細胞の生着を増強するための方法および組成物 Download PDFInfo
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Abstract
Description
本出願は、U.S.S.N. 60/773,405(2006年2月14日提出)(この記載内容は各々、参照により本明細書中で援用される)の35 U.S.C. § 119(e)下での利益を主張する。
本発明は、幹細胞療法改善のための方法および組成物、特に、サブオプティマル用量の造血幹細胞の生着を促進するための方法および組成物に関する。
造血幹細胞移植(HSCT)は、広範な多数の血液学的障害の処置の重要な構成成分である。一般的に、2種類のHSCTが存在する:即ち、自己由来および同種異系移植である。自己由来移植は、骨髄破壊的処置後のレシピエント自身の細胞の注入を包含する。自己由来細胞移植片は、移植片対宿主病(GVHD)の危険を最小限にし、そして合併症低減を生じる。同種異系移植は、典型的にはレシピエントのMHCと適合性であるドナーを用いるドナー幹細胞の注入を包含する。しかしながら適合性非血縁ドナー(MUD)移植片は、より強力な移植片対宿主反応にも関連し、したがってより高い死亡率を生じる。
本発明の開示に従って、幹細胞移植を改善するための方法、組成物およびキットが記載される。特に、造血幹細胞(HSC)の生着を促進するための方法であって、HSC移植片と一緒に移植患者に骨髄前駆細胞(MP)移植片を投与することを包含する方法が提供される。MP移植片は、HSC移植片にとっておよび/または患者にとって自己由来であるかまたは同種異系であり、そしてさらに同種異系MP細胞の混合集団を含み得る。好ましい実施形態では、MP細胞は、投与前にin vitroで増幅される。
5.添付の図面の簡単な説明
6.1 定義
本発明の開示に関して、本明細書中の記載で用いられる技術および科学用語は、特に別記しない限り、当業者により一般に理解される意味を有する。したがって以下の用語は、以下の意味を有するよう意図される:
本発明の開示は、幹細胞生着を促進するための方法、組成物およびキットを記載する。一態様では、それを必要とする患者におけるHSCの生着を増強するための方法であって、患者に(MP)細胞を投与することを包含する方法が提供される。本明細書中で初めて実証されたように、MP細胞はHSCの生着を増強し、それにより、特にHSC移植片が細胞数および/またはHLA不適合に関して最適以下である場合、HSC移植片を受容している移植患者の生存を改善する。
種々の補助的処置は、本明細書中に記載される方法とともに用いられ得る。一態様では、補助的処置としては、特に、抗真菌剤、抗細菌剤および抗ウイルス剤が挙げられる。
本明細書中に記載される方法は、HSC生着を増強するためのキットにより促進され得る。キットは、細胞、例えばHSC、MP(これらに限定されない)、例えば増幅および/または単離細胞、および/または補助的療法用化合物、HSCおよびMPを単離または増幅するための手段、患者に細胞を投与するための手段、あるいはその任意の組合せを含有し得る。キットは、製薬上許容可能な担体、生理学的に許容可能な担体、使用説明書、容器、投与のための器、抗体のいずれかまたはすべて、あるいはその任意の組合せを任意に包含し得る。標識は、典型的にはキットに添付し、そして書かれているかまたは記録された任意の構成要素(これは電子的またはコンピューター読取り可能形態(例えばディスク、光学ディスク、メモリーチップまたはテープ)であり得る)を含み、使用説明書またはキット内容物の使用のためのその他の情報を提供する。
本発明の教示の態様は、以下の実施例を考慮に入れてさらに理解され得るが、これらは如何なる点でも本発明の教示の範囲を限定するよう意図されるべきでない。
マウスからのHSCまたはMPの調製 マウス骨髄細胞を得るために、動物を安楽死させて、大腿骨/脛骨を取り出し、筋肉を取り除く。乳鉢と乳棒を用いて、骨を押し潰してパルプ状にして、骨髄をナイロンスクリーンを通して濾過し、次に1200 RPMで5分間遠心分離する。細胞を、氷上で3〜4分間、1 mlのACK溶液(0.3 MNH4Cl、0.2 MKHCO3、MiliQ濾過水)中に再懸濁し、次に、試験管に染色媒質(2%FCSおよび2 mMEDTA、w/oカルシウム、w/oマグネシウム、w/oフェノールレッドを含有するハンクス緩衝生理食塩水)を充填することにより洗浄する。細胞を遠心分離し、濾過し、染色媒質中に再懸濁して、マウスIgG(1 mg/mlストックの1:50希釈液、Sigma, St. Louis, MO)を付加する。細胞を氷上で10〜15分間インキュベートして、次に染色媒質中の100 μl/マウスの最終容積中に10 μl/マウスの容積でCD117マイクロビーズ(Miltenyi Biotech, Auburn CA)と混合する。細胞を、氷上で25分間インキュベートする。細胞を洗浄し、最終容積〜1 ml/マウスで染色媒質中に再懸濁して、ナイロンスクリーンを通して濾過する。posseld設定を用いて、メーカーの指示に従って、AMAC(Miltenyi, Auburn, CA)を用いて、細胞を濃化する。濃化後、適切な濃度で付加される以下の指示接合抗体(eBioscience, San Diego, CA)とともに染色媒質中に約1×108細胞/mlで細胞を再懸濁する:Sca-1アロフィコシアニン(APC)、c-kitR-フィコエリトリン-シアニン7タンデム(PE-Cy7)、Thy-1.1フルオレセインイソチオシアネート(FITC)、系統(CD3、CD4、CD5、CD8、B220、mac-1、Gr-1およびTer119)R-フィコエリトリン(PE)。細胞を氷上で25分間インキュベートし、洗浄し、遠心分離し、そして染色媒質中に再懸濁する。ヨウ化プロピジウム(PI)を付加して、死細胞を除外する。マウスKTLS-HSC、c-kithighThylowSca-1pos系統negまたはマウスMPc-kithighThynegSca-1neg系統neg/lowをFACSにより単離する。
レシピエントマウスの100%において放射線防護を提供するためにHSCが不適切数で提供された場合にMPが生存を改善し得るか否かを確定するために、これらの試験を設計した。これらの試験は、MPが、同種同系(図3)、適合非血縁ドナー(MUD)(図4)、または完全不適合同種異系設定(図5)での精製HSC移植後の回復を増大し得るか否かを調べた。これらの試験において、各試験に関するHSCおよびMPは、同一ドナーに由来した。
HSC用量が放射線防護を提供するために必要とされる用量より低い場合に、同種異系培養由来MPの含入が適合非血縁ドナー(MUD)HSC移植後の生存率を改善し得たか否かを確定するために、この試験を設計した。
Claims (20)
- 患者における造血幹細胞移植片の生着の増強方法であって、造血幹細胞の生着を増強するのに有効な量で前記患者に骨髄前駆体(MP)細胞移植片を投与することを包含する方法。
- 前記造血幹細胞移植片がサブオプティマル移植片である請求項1記載の方法。
- 上記サブオプティマル移植片が約5.0×106未満のCD34+造血幹細胞(HSC)/患者体重1 kgを含む請求項2記載の方法。
- 上記サブオプティマル移植片が約1.0×106未満のCD34+HSC/患者体重1 kgを含む請求項2記載の方法。
- 前記サブオプティマル移植片が末梢血または骨髄から得られる請求項2記載の方法。
- 前記サブオプティマル移植片が臍帯血(UBC)から得られる請求項2記載の方法。
- 前記サブオプティマル移植片が約4×107未満の有核細胞/患者体重1 kgを含む請求項6記載の方法。
- 前記サブオプティマル移植片が約4.0×105未満のCD34+細胞/患者体重1 kgを含む請求項6記載の方法。
- 前記サブオプティマル移植片が2未満の臍帯血単位由来のHSCを含む請求項6記載の方法。
- 前記サブオプティマル移植片が単一臍帯血単位由来のHSCを含む請求項6記載の方法。
- 前記MP細胞移植片および前記HSC移植片が前記患者に関して同種異系である請求項1記載の方法。
- 前記同種異系移植片が前記患者に関してMHCで少なくとも部分的不適化される請求項11記載の方法。
- 前記同種異系移植片が前記患者に関してMHCで完全不適合化される請求項11記載の方法。
- 前記同種異系移植片が前記患者に関して1つまたは複数のMHC抗原で不適合化される請求項11記載の方法。
- 前記同種異系移植片が前記患者に関してMHCで完全適性化される請求項11記載の方法。
- 前記骨髄前駆細胞移植片が前記造血幹細胞移植片と同時に投与される請求項1記載の方法。
- 前記骨髄前駆細胞移植片が前記造血幹細胞移植片の12時間以内に投与される請求項1記載の方法。
- 前記骨髄前駆細胞移植片が増殖骨髄前駆細胞を含む請求項1記載の方法。
- 前記増殖骨髄前駆細胞が同種異系骨髄前駆細胞の混合物である請求項18記載の方法。
- 前記同種異系骨髄前駆細胞が造血幹細胞移植片に関してMHCで少なくとも部分的不適合化される請求項19記載の方法。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2020511464A (ja) * | 2017-03-15 | 2020-04-16 | オルカ バイオシステムズ インコーポレイテッド | 造血幹細胞移植用の組成物および方法 |
Families Citing this family (26)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105168250B (zh) | 2004-10-25 | 2019-02-05 | 塞勒兰特治疗公司 | 增殖骨髓细胞群体的方法及其应用 |
WO2008137901A2 (en) | 2007-05-06 | 2008-11-13 | Sloan Kettering Institute For Cancer Research | Methods for treating and preventing gi syndrome and graft versus host disease |
EP2442837B1 (en) * | 2009-06-18 | 2014-08-20 | MC2 Cell Aps | Bone marrow extracellular matrix extract and therapeutic use thereof |
US20130287750A1 (en) * | 2009-10-14 | 2013-10-31 | Cellect Biotechnology Ltd. | Method of selecting stem cells and uses thereof |
EP2555781A1 (en) | 2010-04-09 | 2013-02-13 | Fred Hutchinson Cancer Research Center | Compositions and methods for providing hematopoietic function |
EP2555782A1 (en) | 2010-04-09 | 2013-02-13 | Fred Hutchinson Cancer Research Center | Compositions and methods for providing hematopoietic function without hla matching |
EP2729560A4 (en) * | 2011-07-06 | 2014-12-03 | Cellerant Therapeutics Inc | MEGAKARYOCYTE PRE-PROVIDER CELLS FOR THE PRODUCTION OF BLOOD PLATES |
CA2858069C (en) | 2011-12-08 | 2020-02-11 | Fred Hutchinson Cancer Research Center | Compositions and methods for enhanced generation of hematopoietic stem/progenitor cells |
WO2013130499A1 (en) * | 2012-02-29 | 2013-09-06 | University Of Virginia Patent Foundation | Compositions and methods for cxcr4 signaling and umbilical cord blood stem cell engraftment |
WO2013155347A1 (en) | 2012-04-11 | 2013-10-17 | Izumi Raquel | Bruton's tyrosine kinase inhibitors for hematopoietic mobilization |
EP2854850B1 (en) * | 2012-05-25 | 2021-05-26 | Sloan Kettering Institute For Cancer Research | Compositions for treating or preventing radiation disease and gi syndrome |
US9956249B2 (en) | 2013-01-08 | 2018-05-01 | Fred Hutchinson Cancer Research Center | Compositions and methods for expansion of embryonic hematopoietic stem cells |
WO2015052716A1 (en) * | 2013-10-09 | 2015-04-16 | Cellect Biotechnology Ltd. | Activation of hematopoietic progenitors by pretransplant exposure to death ligands |
WO2015057992A1 (en) | 2013-10-16 | 2015-04-23 | Izumi Raquel | Btk inhibitors for hematopoietic mobilization |
KR20160079854A (ko) | 2013-10-31 | 2016-07-06 | 프레드 헛친슨 켄서 리서치 센터 | 변형된 조혈 줄기/선조 및 비-t 효과기 세포 및 이의 용도 |
EP3247808B1 (en) | 2015-01-21 | 2021-05-05 | Fred Hutchinson Cancer Research Center | Point-of-care and/or portable platform for gene therapy |
US11827904B2 (en) | 2015-04-29 | 2023-11-28 | Fred Hutchinson Cancer Center | Modified stem cells and uses thereof |
US20180355318A1 (en) | 2015-04-29 | 2018-12-13 | Fred Hutchinson Cancer Research Center | Modified hematopoietic stem/progenitor and non-t effector cells, and uses thereof |
WO2017096347A1 (en) | 2015-12-04 | 2017-06-08 | Fred Hutchinson Cancer Research Center | Uses of expanded populations of hematopoietic stem/progenitor cells |
WO2017203520A1 (en) * | 2016-05-22 | 2017-11-30 | Yeda Research And Development Co. Ltd. | Methods of using pulmonary cells for transplantation and induction of tolerance |
SG11201908624SA (en) | 2017-04-12 | 2019-10-30 | Magenta Therapeutics Inc | Aryl hydrocarbon receptor antagonists and uses thereof |
JP2021503008A (ja) * | 2017-10-31 | 2021-02-04 | マジェンタ セラピューティクス インコーポレイテッドMagenta Therapeutics, Inc. | 造血幹細胞および前駆細胞移植療法のための組成物および方法 |
US11285177B2 (en) | 2018-01-03 | 2022-03-29 | Globus Medical, Inc. | Allografts containing viable cells and methods thereof |
EP4268831A3 (en) | 2018-09-12 | 2024-05-22 | Fred Hutchinson Cancer Center | Reducing cd33 expression to selectively protect therapeutic cells |
WO2023150393A2 (en) | 2022-02-07 | 2023-08-10 | Ensoma, Inc. | Inhibitor-resistant mgmt modifications and modification of mgmt-encoding nucleic acids |
EP4338745A1 (en) * | 2022-09-14 | 2024-03-20 | Technische Universität Dresden | Allogeneic human macrophages for cell therapy |
Family Cites Families (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2035317T5 (es) * | 1987-11-09 | 1998-03-16 | Becton Dickinson Co | Metodo para analizar celulas hematopoyeticas en una muestra. |
US6852313B1 (en) | 1989-10-16 | 2005-02-08 | Amgen Inc. | Method of stimulating growth of melanocyte cells by administering stem cell factor |
US5061620A (en) * | 1990-03-30 | 1991-10-29 | Systemix, Inc. | Human hematopoietic stem cell |
US5840580A (en) * | 1990-05-01 | 1998-11-24 | Becton Dickinson And Company | Phenotypic characterization of the hematopoietic stem cell |
US6326198B1 (en) * | 1990-06-14 | 2001-12-04 | Regents Of The University Of Michigan | Methods and compositions for the ex vivo replication of stem cells, for the optimization of hematopoietic progenitor cell cultures, and for increasing the metabolism, GM-CSF secretion and/or IL-6 secretion of human stromal cells |
US5199942A (en) * | 1991-06-07 | 1993-04-06 | Immunex Corporation | Method for improving autologous transplantation |
EP0652943B1 (en) * | 1992-07-10 | 2008-07-02 | University Of Pittsburgh | Hematopoietic facilitatory cells and their uses |
US6103522A (en) * | 1994-07-20 | 2000-08-15 | Fred Hutchinson Cancer Research Center | Human marrow stromal cell lines which sustain hematopoiesis |
US5925567A (en) * | 1995-05-19 | 1999-07-20 | T. Breeders, Inc. | Selective expansion of target cell populations |
US5877299A (en) * | 1995-06-16 | 1999-03-02 | Stemcell Technologies Inc. | Methods for preparing enriched human hematopoietic cell preparations |
WO1997033978A1 (en) * | 1996-03-12 | 1997-09-18 | Life Technologies, Inc. | Hematopoietic cell culture nutrient supplement |
US6335195B1 (en) | 1997-01-28 | 2002-01-01 | Maret Corporation | Method for promoting hematopoietic and mesenchymal cell proliferation and differentiation |
US6563332B2 (en) | 1997-08-21 | 2003-05-13 | Ibiden Co., Ltd. | Checker head |
US6908763B1 (en) | 1997-08-22 | 2005-06-21 | The Board Of Trustees Of The Leland Stanford Junior University | Mammalian common lymphoid progenitor cell |
CA2309919A1 (en) * | 1997-11-14 | 1999-05-27 | The General Hospital Corporation | Treatment of hematologic disorders |
JP2002502599A (ja) | 1998-02-05 | 2002-01-29 | ノバルティス アクチエンゲゼルシャフト | 増殖され遺伝子的に修飾されたヒト造血幹細胞集団 |
US6464850B1 (en) | 1998-07-31 | 2002-10-15 | Biowhittaker Molecular Applications, Inc. | Method for producing hydrophilic monomers and uses thereof |
US20030060425A1 (en) * | 1998-11-24 | 2003-03-27 | Ahlem Clarence N. | Immune modulation method using steroid compounds |
WO2000070022A2 (en) | 1999-05-14 | 2000-11-23 | City Of Hope | Ex vivo expansion of mammalian hematopoietic stem cells |
US6761883B2 (en) * | 1999-06-29 | 2004-07-13 | The Board Of Trustees Of The Leland Stanford Junior University | Mammalian myeloid progenitor cell subsets |
AU774876B2 (en) * | 1999-06-29 | 2004-07-08 | Board Of Trustees Of The Leland Stanford Junior University | Mammalian myeloid progenitor cell subsets |
WO2001052649A1 (en) * | 2000-01-18 | 2001-07-26 | The Board Of Trustees Of The Leland Stanford Junior University | Expansion of stem and progenitor cells by beta-catenin |
AU2003272369A1 (en) | 2002-09-13 | 2004-04-30 | The Board Of Trustees Of The Leland Stanford Junior University | Mammalian megakaryocyte progenitor cell |
WO2004046312A2 (en) | 2002-11-15 | 2004-06-03 | The Board Of Trustees Of The University Of Illinois | Methods for in vitro expansion of hematopoietic stem cells |
WO2004071443A2 (en) | 2003-02-12 | 2004-08-26 | Irm Llc | Methods and compositions for modulating stem cells |
US20050215473A1 (en) * | 2003-05-09 | 2005-09-29 | Enrique Alvarez | Prophylactic and therapeutic uses of FGF-20 in radiation protection |
KR20050047500A (ko) * | 2003-11-17 | 2005-05-20 | 오일환 | 중간엽기질세포를 이용한 생착증진 방법 |
CN1635113A (zh) * | 2003-12-31 | 2005-07-06 | 中山大学 | 从人间质干细胞制备造血干细胞的方法 |
CN105168250B (zh) * | 2004-10-25 | 2019-02-05 | 塞勒兰特治疗公司 | 增殖骨髓细胞群体的方法及其应用 |
US7811815B2 (en) * | 2004-11-15 | 2010-10-12 | The Board Of Trustees Of The Leland Stanford Junior University | Therapeutic uses of allogeneic myeloid progenitor cells |
-
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Non-Patent Citations (2)
Title |
---|
JPN6012043699; BITMANSOUR,A. et al: 'Myeloid progenitors protect against invasive aspergillosis and Pseudomonas aeruginosa infection foll' Blood Vol.100, No.13, 2002, p.4660-7 * |
JPN6012043700; ARBER,C. et al. Blood, 2003, Vol.102, No.11, Part 1, p.941A * |
Cited By (2)
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JP2020511464A (ja) * | 2017-03-15 | 2020-04-16 | オルカ バイオシステムズ インコーポレイテッド | 造血幹細胞移植用の組成物および方法 |
JP7483087B2 (ja) | 2017-03-15 | 2024-05-14 | オルカ バイオシステムズ インコーポレイテッド | 造血幹細胞移植用の組成物および方法 |
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IL193345A0 (en) | 2011-08-01 |
CN101421393A (zh) | 2009-04-29 |
US20070237752A1 (en) | 2007-10-11 |
AU2007214468B2 (en) | 2013-04-04 |
CA2642020A1 (en) | 2007-08-23 |
WO2007095594A2 (en) | 2007-08-23 |
EP1984491B1 (en) | 2016-12-07 |
JP5341525B2 (ja) | 2013-11-13 |
CA2642020C (en) | 2014-10-07 |
EP1984491A4 (en) | 2010-03-24 |
CN101421393B (zh) | 2013-08-14 |
AU2007214468A1 (en) | 2007-08-23 |
IL193345A (en) | 2012-10-31 |
US8383095B2 (en) | 2013-02-26 |
EP1984491A2 (en) | 2008-10-29 |
WO2007095594A3 (en) | 2008-07-31 |
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