JP2009096739A - B細胞悪性リンパ腫治療薬 - Google Patents
B細胞悪性リンパ腫治療薬 Download PDFInfo
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Abstract
【解決手段】本発明に係るB細胞悪性リンパ腫治療薬は、抗HMGB1モノクローナル抗体を有効成分とすることを特徴とする。
【選択図】なし
Description
(a)ラットの免疫
市販のウシ胸腺由来HMGB1とHMGB2との混合物(和光純薬工業社製、コード番号:080−070741)1mg/mLを2mLガラス製注射筒にとり、別の2mLガラス製注射筒にとった等容量のフロイント完全アジュバンドと連結管を通じて徐々に混和することによって、エマルションとした。セボフルレンにより麻酔したラットの後肢足蹠に、得られたエマルションを0.1mLずつ、計0.2mL注射投与した。2週間後、頚静脈から試験採血し、抗体価の上昇を確認した。次いで、腫大した腸骨リンパ節を前記注射投与から5週間後に無菌的に取り出した。得られた2個のリンパ節から、約6×107個の細胞を回収することができた。
上記腸骨リンパ節細胞とマウスミエローマSP2/O−Ag14(SP2)細胞を、ポリエチレングリコールを用いて融合させ、得られた融合細胞を96穴マイクロプレートに蒔いた。1週間後、最初のELISAスクリーニングを行ない、陽性ウェルについて、ウェスタンブロットにより二次スクリーニングを行なった。陽性を示すウェル細胞を24穴マイクロプレートに移し、細胞をほぼコンフルエントな状態(約2×105個)に殖やしてから、0.5mLの凍結培地(GIT培地にウシ胎児血清を10%とジメチルスルホキシドを10%添加したもの)を用いて、液体窒素中で凍結保存した。この凍結保存細胞を解凍した後、96穴マイクロプレートでクローニングした。
回転培養装置(Vivascience社製)により上記陽性細胞を2週間大量培養し、濃度2〜3mg/mLの抗体液を得た。この抗体液をアフィニティゲル(インビトロジェン社製、MEP−HyperCel)と中性pH下で混和し、抗HMGB1抗体をゲルへ特異的に結合させた。特異的にゲルに結合した抗体を、グリシン−塩酸バッファー(pH4)により溶出した。溶出液を限外濾過装置により濃縮した後、セファロースCL6Bゲル濾過カラム(直径2cm×長さ97cm)によって、さらに精製した。
液体培地(ニッスイ社製、製品名「RPMI 1640」)に、別途調製したヒトHMGB1を1×10-10〜1×10-6g/mLの濃度で溶解した。また、比較のためにHMGB1を添加しない培地も用意した。これら培地(1mL)を直径2cmのシャーレに加え、さらにB細胞悪性リンパ腫株であるFL18とFL218(医仁会武田総合病院の大野仁嗣先生より入手)をそれぞれ約20万個/mLの割合で添加した。なお、FL18はヒトB細胞悪性リンパ腫株であり、FL218は、アポトーシスの抑制作用を有するBcl−2遺伝子が欠損したFL18である。これらB細胞悪性リンパ腫株を37℃で48時間培養した後、各培地における細胞の濃度を顕微鏡で観察することにより測定した。FL18の結果を図1(1)に、FL218の結果を図1(2)に示す。なお、図1中の「*」は、得られた結果をDunnet’sテストにおいて検定した場合にp<0.05で有意差がある場合を示し、「**」はp<0.01で有意差がある場合を示す。
実施例1で得た抗HMGB1モノクローナル抗体を1μg/mLの濃度で液体培地に溶解した以外は上記実施例2と同様にして、2種のB細胞悪性リンパ腫株を37℃で48時間培養した。培養開始直後、並びに培養開始から2時間後、6時間後、18時間後、24時間後および48時間後における各培地の細胞の濃度を、上記実施例2と同様に測定した。FL18の結果を図2(1)に、FL218の結果を図2(2)に示す。
Claims (3)
- 抗HMGB1モノクローナル抗体を有効成分とすることを特徴とするB細胞悪性リンパ腫治療薬。
- 抗HMGB1モノクローナル抗体を、1回当たり0.2〜5mg/(kg体重)投与するものである請求項1に記載のB細胞悪性リンパ腫治療薬。
- 静脈注射投与するものである請求項1または2に記載のB細胞悪性リンパ腫治療薬。
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JP2009096739A true JP2009096739A (ja) | 2009-05-07 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2011037227A1 (ja) * | 2009-09-28 | 2011-03-31 | 国立大学法人岡山大学 | アテローム動脈硬化抑制剤 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003520763A (ja) * | 1999-02-11 | 2003-07-08 | ノース・ショア−ロング・アイランド・ジューイッシュ・リサーチ・インスティテュート | 炎症症状を治療するためのhmg1のアンタゴニスト |
WO2006113909A2 (en) * | 2005-04-19 | 2006-10-26 | Seattle Genetics, Inc. | Humanized anti-cd70 binding agents and uses thereof |
WO2007062090A2 (en) * | 2005-11-23 | 2007-05-31 | Genentech, Inc. | Methods and compositions related to b cell assays |
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- 2007-10-15 JP JP2007267948A patent/JP5224325B2/ja not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JP2003520763A (ja) * | 1999-02-11 | 2003-07-08 | ノース・ショア−ロング・アイランド・ジューイッシュ・リサーチ・インスティテュート | 炎症症状を治療するためのhmg1のアンタゴニスト |
WO2006113909A2 (en) * | 2005-04-19 | 2006-10-26 | Seattle Genetics, Inc. | Humanized anti-cd70 binding agents and uses thereof |
WO2007062090A2 (en) * | 2005-11-23 | 2007-05-31 | Genentech, Inc. | Methods and compositions related to b cell assays |
Non-Patent Citations (1)
Title |
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JPN6012056899; Akihiko Taguchi et al.: Nature Vol.405, 20000518, p.354-360 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011037227A1 (ja) * | 2009-09-28 | 2011-03-31 | 国立大学法人岡山大学 | アテローム動脈硬化抑制剤 |
JP2011068627A (ja) * | 2009-09-28 | 2011-04-07 | Okayama Univ | アテローム動脈硬化抑制剤 |
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