JP2016502980A - 呼吸器系疾患を治療又は予防する方法 - Google Patents
呼吸器系疾患を治療又は予防する方法 Download PDFInfo
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Abstract
Description
本出願は、2012年12月12日に出願された「Methods of treating or preventing respiratory conditions」と題される米国特許出願第61/736352号の優先権を主張する。当該出願の内容全体は、参照により本明細書に組み込まれる。
本開示は、呼吸器系疾患(respiratory conditions)、例えば、IgE媒介性(IgE-mediated)のアレルギー性呼吸器系疾患などを治療又は予防するための方法に関する。
呼吸器系疾患は、ガス交換に関与する臓器及び組織に影響を及ぼす病的状態を包含するものと認識され、上気道、気管、気管支、細気管支、肺胞、胸膜及び胸膜腔、並びに呼吸の神経及び筋肉の状態を含む。慢性呼吸器系疾患は、世界中の総死者数のおよそ7%にあたる死者をもたらし、世界疾病負担の約4%に相当する。慢性呼吸器系疾患のコストは、米国単独で、直接及び間接コストを含めて毎年約1,540億USドルであると見積もられる。呼吸器系疾患は、以下を含む複数のクラスに分類できる:
・炎症性肺疾患(lung conditions)、例えば、喘息、嚢胞性線維症、肺気腫、慢性閉塞性肺疾患又は急性呼吸窮迫症候群などであって、対象の肺における好中球及び/又は炎症性サイトカインレベルの上昇により特徴付けられるもの;
・閉塞性肺疾患、例えば、慢性閉塞性肺疾患及び喘息などであって、気道容積の低下又は自由なガス流の障害により特徴付けられるもの;及び
・拘束性肺疾患(間質性肺疾患としても知られる)、例えば、乳児呼吸窮迫症候群などであって、不完全な肺拡張及び/又は肺の硬さの高まりを引き起こす肺コンプライアンスの喪失により特徴付けられるもの。
本発明者らは、現在、喘息(例えば、アレルギー性喘息)などのヒト呼吸器系疾患の受け入れられている動物モデルにおいて、STRO-1+細胞調製物を用いて、用量依存性の様式で、TH2媒介性アレルギー反応(例えば、IgE媒介性アレルギー反応)を低下(例えば、好酸球及び/又はIL-4レベル及び/又はIgEレベルを低下)させることができ、且つ気管支過敏性を低下させることができることを示している。本発明者らは、それらが、早期(early)アレルギー反応及び/又は遅発性(late)アレルギー反応のいずれか(又は両方)を抑制できることを発見した。この用量反応性は、STRO-1+細胞調製物が治療的有用性を提供していることを実証する。
(i)対象が、持続的に、喘鳴し始め、及び/又は咳をし始め、及び/又は胸部圧迫感を有し始め、及び/又は呼吸困難を有し始める;
(ii)対象が、スパイロメーターにより評価した場合に、以下の1つ以上を示す:
a)少なくとも2週間、週に少なくとも3日間で20%の差異;
b)例えば、
吸入βアゴニスト(例えば、サルブタモール)を10分間;
吸入コルチコステロイド(例えば、ベクロメタゾン)を6週間;
30 mgのプレドニゾロンを14日間
などの治療後、≧20%のピークフローの改善;
c)トリガー(例えば、エクササイズ)への暴露後、≧20%のピークフローの低下;
(iii)気管支鏡検査により、異常な細胞及び/又は外来物質及び/又は対象の気道閉塞が示される;又は
(iv)胸部CTスキャンにより、肺血管の異常、肺における血液又は体液の貯留、気管支拡張症、胸水又は肺炎が示される。
(i)例えば気管支チャレンジテストを用いて評価されるような、気管支過敏性の改善;
(ii)気道過敏性の改善;
(iii)肺又は気管支肺胞洗浄液の好酸球浸潤の低下;
(iv)肺又は気管支肺胞洗浄液の好中球浸潤の低下;
(v)例えばスパイロメーターにより評価されるような、遅発性喘息反応の低下;
(vi)例えばスパイロメーターにより評価されるような、早期喘息反応の低下;及び/又は
(vii)例えば胸部CTスキャンにより評価されるような、肺リモデリング/線維症の低下。
一般的技術及び選択された定義
本明細書を通じて、特記のない限り、又は文脈がそうでないことを要求する場合を除き、単一の工程、組成物、工程の群又は組成物の群への言及は、1及び複数(すなわち、1以上)のそれらの工程、組成物、工程の群又は組成物の群を包含すると解されるものとする。
・メジャー基準(4つ全てが必要):
○間質性肺疾患の他に知られた原因の排除(薬物、暴露、結合組織疾患);
○拘束性(肺活量の低下)及びガス交換障害(pO2, p(A-a)O2, DLCO)の所見を有する肺機能検査異常;
○高分解能CT(high-resolution CT)スキャンで最小のすりガラス様を有する両肺底部の網状の異常;及び
○経気管支肺生検又は気管支肺胞洗浄(BAL)で代替的診断を支持する特徴が示されないこと。
・マイナー基準(4つのうち3つが必要):
○年齢>50歳;
○他の理由では説明できない労作時呼吸困難の潜行性の発症;
○病気の期間が>3ヶ月;及び
○両側肺野の吸気性クラックル。
一例において、本開示は、アレルゲンに対する反応(例えば、アレルギー反応)を低下させる又は予防するための方法を提供する。本明細書で使用する場合、用語「アレルゲン」とは、特異的なIgE形成(すなわちアレルギー反応)を誘導することができる1つ以上の抗原を含む物質を意味すると解されるものとする。IgEの生成後、IgEはマスト細胞又は好塩基球の表面上のFc受容体と結合する。その後のアレルゲンへの暴露後、アレルゲンの少なくとも2つのエピトープと結合した少なくとも2つのIgE抗体が、IgE分子のFab'領域の架橋を引き起こし、マスト細胞又は好塩基球において様々な血管作用性アミン(例えば、ヒスタミン)の放出がもたらされ、これによりアレルギー症状が誘導される。用語アレルゲンは、すべてのタイプのアレルゲン、例えば、ポリペプチドアレルゲン、リン脂質アレルゲン、脂肪酸又は炭水化物などを含む。一般的なアレルゲンの例を表1に記載する。
STRO-1+細胞は、骨髄、血液、乳歯(例えば、脱落乳歯)、歯髄細胞、脂肪組織、皮膚、脾臓、膵臓、脳、腎臓、肝臓、心臓、網膜、脳、毛包、腸、肺、リンパ節、胸腺、骨、靱帯、腱、骨格筋、真皮、及び骨膜で見られる細胞である。
一例において、STRO-1+細胞及び/又はその子孫細胞は、例えば目的のタンパク質を発現及び/又は分泌するために、遺伝子改変される。例えば、細胞は、呼吸器系疾患の治療に有用なタンパク質、例えば、プロテアーゼ、DNアーゼ(DNAse)又はサーファクタントタンパク質(例えば、サーファクタントタンパク質C)などを発現するよう操作される。
呼吸器系疾患の発症又は進行を治療又は予防又は遅延させる細胞又は可溶性因子の能力を測定するための方法は、当業者に明らかだろう。
(i)呼吸器系疾患に罹患した試験対象に細胞又は可溶性因子を投与すること、及び呼吸器系疾患の症状を評価すること;
(ii)(i)における対象の呼吸器系疾患症状レベルを、該細胞又は可溶性因子を投与されていない、呼吸器系疾患に罹患したコントロール対象の呼吸器系疾患症状と比較すること、
を含み、
ここで、該コントロール対象と比較して、該試験対象における症状の改善が、該細胞又は可溶性因子が呼吸器系疾患を治療することを示す、方法を提供する。
本開示の一例において、STRO-1+細胞及び/又はその子孫細胞は、組成物の形態で投与される。一例において、かかる組成物は医薬上許容される担体及び/又は賦形剤を含む。
一例において、STRO-1+細胞由来の及び/又は子孫細胞由来の上清又は可溶性因子は、組成物の形態、例えば適切な担体及び/又は賦形剤を含む組成物の形態で投与される。一例において、担体又は賦形剤は、可溶性因子又は上清の生物学的効果に悪影響を及ぼさない。
STRO-1+細胞由来の上清又は可溶性因子、STRO-1+細胞又はその子孫は、他の有益な薬物又は生物学的分子(増殖因子、栄養因子)とともに投与されてよい。他の薬剤とともに投与される場合、それらは、単一医薬組成物又は別個の医薬組成物で、同時に、又は該他の薬剤と連続して(該他の薬剤の投与の前又は後のいずれか)、一緒に投与されてよい。共投与されてよい生物活性因子には、抗アポトーシス剤(例えば、EPO、EPOミメチボディ、TPO、IGF-I及びIGF-II、HGF、カスパーゼ阻害剤);抗炎症剤(例えば、p38 MAPK阻害剤、TGFベータ阻害剤、スタチン、IL-6及びIL-1阻害剤、ペミロラスト、トラニラスト、レミケード、シロリムス及びNSAID(非ステロイド性抗炎症薬;例えば、テポキサリン、トルメチン、スプロフェン);免疫抑制/免疫調節剤(例えば、カルシニューリン阻害剤、例えば、シクロスポリン、タクロリムスなど;mTOR阻害剤(例えば、シロリムス、エベロリムス);抗増殖剤(例えば、アザチオプリン、ミコフェノール酸モフェチル);コルチコステロイド(例えば、プレドニゾロン、ヒドロコルチゾン);抗体、例えば、モノクローナル抗IL-2Rアルファ受容体抗体(例えば、バシリキシマブ、ダクリズマブ)、ポリクローナル抗T細胞抗体(例えば、抗胸腺細胞グロブリン(ATG);抗リンパ球グロブリン(ALG);モノクローナル抗T細胞抗体OKT3));抗血栓形成剤(例えば、ヘパリン、ヘパリン誘導体、ウロキナーゼ、PPack(デキストロフェニルアラニンプロリンアルギニンクロロメチルケトン)、抗トロンビン化合物、血小板受容体アンタゴニスト、抗トロンビン抗体、抗血小板受容体抗体、アスピリン、ジピリダモール、プロタミン、ヒルジン、プロスタグランジン阻害剤及び血小板阻害剤);及び抗酸化剤(例えば、プロブコール、ビタミンA、アスコルビン酸、トコフェロール、コエンザイムQ-10、グルタチオン、L-システイン、N-アセチルシステイン)及び局所麻酔薬などが挙げられる。
本開示はまた、本明細書に記載するようないずれかの例に従う方法で使用するため、又は当該方法で使用される場合の医療デバイスを提供する。例えば、本開示は、本明細書に記載するようないずれかの例に従うSTRO-1+細胞及び/又はその子孫細胞及び/又はそれからの可溶性因子及び/又は組成物を含む、シリンジ若しくはカテーテル若しくは吸入具、又は他の適切なデリバリーデバイスを提供する。任意選択で、シリンジ又はカテーテル又は吸入具は、本明細書に記載するようないずれかの例に従う方法で使用するための指示書とともにパッケージされる。
STRO-1+細胞由来の上清又は可溶性因子、STRO-1+細胞又はその子孫は、外科的に移植、注入、吸入、デリバリー(例えば、カテーテル又はシリンジを手段として)されてよく、或いは修復又は増強を必要とする部位、例えば肺に直接的又は間接的に投与されてよい。
骨髄(BM)を、健康な正常成人ボランティア(20〜35歳)から採取する。簡潔には、40 mlのBMを、後腸骨稜から、リチウム-ヘパリン抗凝固剤含有チューブに吸引する。
STRO-1強陽性(bright)細胞を単離するための単一試薬としてSTRO-3 mAbを用いることの可能性を確認するために実験を設計した。
3.1 方法
アレルギー性喘息のハウスダストマイト(HDM)ヒツジモデルは、ヒトと臨床的に関連するアレルゲンを使用することから、喘息に対するMPCの効果を研究するために選択した。他の喘息モデルは不足部分がある。例えば、マウスOVAチャレンジモデルは、ヒトと臨床的に関連しないアレルゲンを使用しており、肺炎症のパターン及び分布はヒトで観察されるものとは異なっており、ヒトにおける慢性喘息とは対照的に、肺及び肺実質の両方の炎症/リモデリングが観察され、気道平滑筋の大幅な増加は観察されない。同様に、喘息の回虫(Ascaris)ヒツジモデルは、臨床的に関連する抗原を使用せず、ヒトでは通常暴露されないアレルゲン(豚回虫(ascaris suum))に対して比較的弱い好酸球反応とともに強い好中球反応を有する。
・血液学及び凝固:赤血球数(RBC)、白血球数(WBC)、ヘモグロビン(Hb)、ヘマトクリット、血小板、好中球、リンパ球、単球、好酸球、好塩基球、フィブリノゲン。
・生化学:ナトリウム、カリウム、塩化物、重炭酸塩、グルコース、クレアチニン、カルシウム、マグネシウム、リン酸塩、総タンパク質、アルブミン、総ビリルビン、アスパラギン酸トランスアミナーゼ(AST)、アラニントランスアミナーゼ(ALT)、γ-グルタミルトランスペプチダーゼ(GGT)。
・サイトカイン試験:サイトカイン(TNF-α及びIFN-γ)。
HDM感作させた喘息ヒツジにおける、処置前(pre-treatment)、oMPC又は生理食塩水の単回静脈内注入から1週間後及び4週間後の初期喘息反応(EAR)
1億5,000万個のoMPCを投与したヒツジは、oMPC処置から4週間後の時点において、アレルゲンチャレンジ後1時間の間、肺機能が有意に改善した(図4A、B及びC)。oMPC処置から4週間後の時点における肺機能の改善は、oMPC処置前のEARと比較した場合、アレルゲンチャレンジ後のEARにおいて57.1%の低下として現れた(p<0.05(図4A及びC))。
生理食塩水コントロールグループは、処置前の値と比較した場合、1週間及び4週間の両方の時点で評価した際にアレルゲンチャレンジから6時間後のLARにおいて増加傾向を示した(図5A)。2,500万個のoMPCで処置したグループは、処置前の値と比較した場合、1週間にて6時間LARの有意な低下と関連した(図5A)。7,500万個及び1億5,000万個のoMPCで処置したグループはすべて、処置前の値と比較した場合、処置から1週間後及び4週間後の両方の時点にて6時間LARにおいて低下傾向が認められた。6時間LARにおける処置グループ間の比較変化を示す要約グラフを図5Bに示す。処置前からその後の(follow-up)処置までの変化%によりLARの相対変化を評価する場合、2,500万個のoMPC用量グループにおけるLARの変化%は、1週間の時点でコントロールと比較して有意に改善した(p<0.05、図5B)。同様の傾向は、oMPCの処置から4週間後の時点での6時間LARについても示された(図5C)。
oMPCの代わりに生理食塩水ビヒクル処置を受けたコントロールグループは、1週間及び4週間の時点で、BHRの有意な変化は認められなかった(図6A、B、C及びD)。7,500万個のoMPCを受けたヒツジグループは、oMPC処置前に測定されたBHRと比較した場合、oMPC処置から1週間後及び4週間後の両方の時点にて有意に改善されたBHR指標を有した(図6A)。処置前と1週間及び4週間の時点との間の差は、すべての処置グループを事後解析(post hoc analysis)にて一緒にプールした場合、統計的に有意であった(図6D)。
気管支肺胞洗浄(BAL)は、oMPC又は生理食塩水コントロール処置のいずれかから1週間及び4週間後におけるアレルゲンチャレンジから2日後にサンプリングした。この試験で使用したすべてのヒツジにおいて、アレルゲンチャレンジ及び幹細胞処置の前にサンプリングした全BAL細胞の好酸球の平均ベースラインパーセンテージは4.5%である。アレルゲンチャレンジから2日後であって、幹細胞又は生理食塩水の処置前にサンプリングしたすべてのヒツジのBAL中の好酸球の平均パーセンテージ(すなわち、BAL好酸球の平均処置前パーセンテージ)は15.0%である。アレルゲンチャレンジから2日後であってoMPC処置後の試験ヒツジから回収されたBAL液中の好酸球の分析により、2,500万個のoMPCを注入したヒツジについて、処置前と1週間の時点との間に有意な差が存在することが明らかとなった(図7A及びB)。7,500万個及び1億5,000万個のoMPCで処置したグループについては、処置前と1週間及び4週間の時点との間におけるBAL液中の好酸球数の差は、統計学的有意に達しなかった。しかしながら、1週間及び4週間の両方の時点において、処置前と処置後との間のBAL好酸球の差は、3つの処置の値をすべて事後解析にてプールした場合、統計学的に有意であった(図7E)。
アレルゲン誘発性の喘息は、アレルゲン特異的IgEと関連することから、すべてのヒツジの血清中の循環HDM特異的IgEのレベルを、oMPC投与前、並びにoMPC処置から1週間後及び4週間後の2つの時点において評価した(図11A)。結果は、1億5,000万個のoMPC用量が、処置前のHDM特異的IgEレベルと比較して、oMPC処置から1週間後にHDM特異的IgEの有意な低下に効果的であったことを示す(図11A)。2,500万個及び7,500万個のoMPC処置は、処置前のHDM特異的IgEレベルと比較して、oMPC処置から4週間後にHDM特異的IgEを有意に低下させた。生理食塩水で処置したコントロールヒツジにおいては、HDM特異的IgEレベルは、処置前の値と比較して、1週間及び4週間の時点でわずかに低下した;しかしながら、この差は有意ではなかった(図11A)。処置前から処置から1週間後及び4週間後までの血清中のIgEレベルの変化%を評価した、コントロールヒツジと、異なる用量のoMPCを注入したヒツジとの比較を図11B及びCに示す。
試験ヒツジの左後葉(left caudal lobe)から剖検時にサンプリングした肺組織に対して免疫組織化学を実施した。細胞表面抗体マーカーパネルを組織切片に使用して、CD4、CD8及びγδ陽性T細胞サブセット、CD45R陽性細胞、並びにIgE陽性細胞(マスト細胞を同定する)を同定した。好酸球は、ペルオキシダーゼ陽性染色細胞として同定した。これらの細胞タイプの相対密度は、以下を含む3つの異なる肺の位置にて評価した:実質(肺胞腔及び肺胞壁などの非気道組織を含んだ);気道壁の粘膜固有層(細胞密度分析を、内腔上皮と気道平滑筋束の内側境界との間の気道壁領域に制限した);並びに全気道壁(気道内腔上皮と、肺胞に接する外側の外膜との間の密度計数を含んだ)。
好酸球顆粒を特徴的な赤色に染色し、バックグラウンド組織を青色に染色することにより好酸球を同定するLuna組織学的方法により肺組織を染色した。
本研究では、ヒツジ喘息モデルにおいて、oMPC療法の安全性及び有効性を評価した。免疫化前(pre-immunization)のレベルと比較して血清中に高レベルのHDM特異的IgE抗体を有するヒツジに、6週間の期間にわたって、HDMで肺全体へのエアロゾルチャレンジを3回行って、気道をHDMに感作させた。ヒツジを4つのグループにランダムに配置し、生理食塩水(コントロール)、又は3つの用量のうち1つのoMPC処置(2,500万個、7,500万個又は1億5,000万個のoMPC)のいずれかをIV注入により与えた。次いで、それら各々のoMPC又は生理食塩水処置から7日後及び28日後に、ヒツジをHDMで再チャレンジした。HDM再チャレンジ後すぐに、先に示した時点において、肺機能及びBAL細胞分析を評価した。2,500万個、7,500万個又は1億5,000万個のoMPCでのoMPCのIV注入は、良好な認容性を示し、これらの細胞の投与と関連する有害事象はなかった。
Claims (25)
- 対象において、呼吸器系疾患を治療若しくは予防する、及び/若しくはIgE媒介性アレルギーを治療するため、及び/若しくはアレルゲンに対するアレルギー反応を低下させるため、及び/若しくはアレルゲンに対してアネルギーを誘導するため、並びに/又はアレルギーに罹患した対象において肺機能を改善するため、の方法であって、STRO-1+細胞が富化された細胞集団及び/又はその子孫及び/又はそれに由来する可溶性因子を該対象に投与することを含む、方法。
- 呼吸器系疾患が、急性呼吸器系疾患又は慢性呼吸器系疾患である、請求項1に記載の方法。
- 呼吸器系疾患が、炎症性呼吸器系疾患、閉塞性呼吸器系疾患又は拘束性呼吸器系疾患である、請求項1又は2に記載の方法。
- 呼吸器系疾患又はアレルギーが、閉塞性呼吸器系疾患若しくはアレルギー、又は炎症性肺疾患若しくはアレルギーである、請求項3に記載の方法。
- 呼吸器系疾患が喘息である、請求項4に記載の方法。
- 喘息が、急性喘息、慢性喘息、重症喘息及び/又は難治性喘息である、請求項5に記載の方法。
- 喘息が、長時間作用性βアゴニスト(LABA)難治性喘息又はステロイド難治性喘息である、請求項6に記載の方法。
- 呼吸器系疾患が拘束性呼吸器系疾患である、請求項3に記載の方法。
- 呼吸器系疾患が特発性肺線維症である、請求項8に記載の方法。
- 疾患がハウスダストマイトアレルゲン(HDM)に対するアレルギーであるか、又はアレルゲンがHDMである、請求項1に記載の方法。
- STRO-1強陽性(bright)細胞が富化された細胞集団及び/又はその子孫及び/又はそれに由来する可溶性因子を投与することを含む、請求項1〜10のいずれか一項に記載の方法。
- STRO-1+細胞が富化された集団及び/又はその子孫及び/又はそれに由来する可溶性因子が全身投与される、請求項1〜11のいずれか一項に記載の方法。
- STRO-1+細胞が富化された集団及び/又はその子孫及び/又はそれに由来する可溶性因子が、静脈内又は鼻腔内に投与される、請求項12に記載の方法。
- 集団及び/又は子孫及び/又は可溶性因子が複数回投与される、請求項1〜13のいずれか一項に記載の方法。
- 対象を含み、且つ以下:
(i)対象が、持続的に、喘鳴し始め、及び/又は咳をし始め、及び/又は胸部圧迫感を有し始め、及び/又は呼吸困難を有し始める;
(ii)対象が、スパイロメーターにより評価した場合に、以下の1つ以上を示す:
a)少なくとも2週間、週に少なくとも3日間で20%の差異;
b)以下での治療後に、≧20%のピークフローの改善:
吸入βアゴニストを10分間;
吸入コルチコステロイドを6週間;
30 mgのプレドニゾロンを14日間;
c)トリガーへの暴露後、≧20%のピークフローの低下;
(iii)気管支鏡検査により、異常な細胞及び/又は外来物質及び/又は対象の気道閉塞が示される;又は
(iv)胸部CTスキャンにより、肺血管の異常、肺における血液又は体液の貯留、気管支拡張症、胸水又は肺炎が示される
の1つ以上が生じた場合に、更なる用量の集団及び/又は子孫及び/又は可溶性因子を投与することを含む、請求項1〜14のいずれか一項に記載の方法。 - 以下:
(i)気管支過敏性の改善;
(ii)肺又は気管支肺胞洗浄液の好酸球浸潤の低下;
(iii)肺又は気管支肺胞洗浄液の好中球浸潤の低下;
(iv)遅発性喘息反応の低下;
(v)早期喘息反応の低下;及び/又は
(vi)肺リモデリング/線維症の低下
の1つ以上を達成するのに十分な用量の集団及び/又は子孫及び/又は可溶性因子を投与することを含む、請求項1〜15のいずれか一項に記載の方法。 - 1×106個〜150×106個の間のSTRO-1+細胞及び/又はその子孫を投与することを含む、請求項1〜16のいずれか一項に記載の方法。
- 全身用量のSTRO-1+細胞及び/又はその子孫及び/又はそれに由来する可溶性因子を投与することを含む、請求項1〜17のいずれか一項に記載の方法。
- 10 mL中150×106個のSTRO-1+細胞及び/又はその子孫を対象に投与することを含む、請求項18に記載の方法。
- STRO-1+細胞が富化された集団及び/又は子孫細胞が、自己性又は同種異系であり、且つ/或いは可溶性因子が、自己性又は同種異系細胞に由来する、請求項1〜19のいずれか一項に記載の方法。
- STRO-1+細胞が富化された集団及び/又は子孫細胞が、投与前に、及び/又は可溶性因子を得る前に、培養増殖されている、請求項1〜20のいずれか一項に記載の方法。
- STRO-1+細胞が富化された集団が、STRO-1強陽性(bri)であり、及び/又は組織非特異型アルカリホスファターゼ(TNAP)を発現しており、且つ/或いは子孫細胞及び/又は可溶性因子が、STRO-1強陽性(bri)であり及び/又はTNAPを発現する、STRO-1+細胞に由来する、請求項1〜21のいずれか一項に記載の方法。
- STRO-1+細胞及び/又はその子孫細胞及び/又はそれに由来する可溶性因子が、該STRO-1+細胞及び/又はその子孫細胞及び/又はそれに由来する可溶性因子と、担体及び/又は賦形剤とを含む組成物の形態で投与される、請求項1〜22のいずれか一項に記載の方法。
- 呼吸器系疾患の治療若しくは予防、並びに/又はアレルギーに罹患した対象における、IgE媒介性アレルギーの治療、及び/若しくはアレルゲンに対するアレルギー反応の低下、及び/若しくはアレルゲンに対するアネルギーの誘導、及び/若しくは肺機能の改善、に使用するための、STRO-1+細胞が富化された細胞集団及び/又はその子孫及び/又はそれに由来する可溶性因子。
- 対象において呼吸器系疾患を治療若しくは予防するため、並びに/又はアレルギーに罹患した対象において、IgE媒介性アレルギーを治療するため、及び/若しくはアレルゲンに対するアレルギー反応を低下させるため、及び/若しくはアレルゲンに対してアネルギーを誘導するため、及び/若しくは肺機能を改善するための、医薬の製造における、STRO-1+細胞が富化された細胞集団及び/又はその子孫及び/又はそれに由来する可溶性因子の使用。
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 413, no. 2, JPN6017031333, 2011, pages 353 - 357, ISSN: 0003623664 * |
J. ALLERRGY CLIN. IMMUNOL., vol. 129, no. 4, JPN6017031332, 2012, pages 1094 - 1101, ISSN: 0003623666 * |
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STEM CELLS, vol. 29, no. 7, JPN6017031331, 2011, pages 1137 - 1148, ISSN: 0003623665 * |
Cited By (1)
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EP4098267A4 (en) * | 2020-01-30 | 2024-03-06 | JCR Pharmaceuticals Co., Ltd. | MEDICINAL COMPOSITION COMPRISING CELLS DERIVED FROM DENTAL PULP |
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