JP2011516582A - Irx−2の改良された作製方法 - Google Patents
Irx−2の改良された作製方法 Download PDFInfo
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Abstract
【選択図】図1
Description
Claims (27)
- 白血球をリンパ球分離培地(LSM)に投入し、そして該培地を自動細胞処理及び洗浄システムで洗浄及び遠心分離して精製された単核細胞(MNC)を得ることによりMNCを精製して汚染細胞を除去し、
該MNCを密閉された無菌バッグシステム内に一晩保存し、
該MNCの誘導混合物をスケーラブルな細胞培養システム内でマイトジェン及びシプロフロキサシンで刺激し、そして該MNCから一次細胞由来バイオロジックを作製し、
該誘導混合物から該マイトジェンをろ過により除去し、
該誘導混合物をインキュベーションし、
該誘導混合物をろ過により清澄して一次細胞由来バイオロジック上澄を得て、
該一次細胞由来バイオロジック上澄から陰イオン交換クロマトグラフィによりDNAを除去し、そして、
該一次細胞由来バイオロジック上澄からウイルスを二段の連続した15ナノメータウイルスろ過で除去する、
工程を含む、一次細胞由来バイオロジックの作製方法。 - 前記精製工程は、さらに、複数のドナーからMNCを同時に精製することを規定する、請求項1に記載の方法。
- 前記精製工程は、さらに、顆粒球及び赤血球の除去を最適化するために、1500〜3000rpmで20分間、遠心分離することを規定する、請求項1に記載の方法。
- 前記遠心分離工程は、さらに、血小板を1.2x1010細胞を下回るレベルまで除去することを規定する、請求項3に記載の方法。
- 前記作製工程は、さらに、IL−2及びIL−1βを10:1の比に作製することを規定する、請求項4に記載の方法。
- 前記刺激工程は、さらに、該MNCの誘導混合物をマイトジェン及び80μg/mLのシプロフロキサシンで刺激することを規定する、請求項1に記載の方法。
- 前記作製工程は、さらに、IL−1β、IL−2及びIFN−γを含むIRX−2を作製することを規定する、請求項1に記載の方法。
- 前記作製工程は、さらに、少なくとも4LのIRX−2を作製することを規定する、請求項7に記載の方法。
- 前記作製工程は、さらに、300〜1800pg/mLのIL−1β、4000〜8000pg/mLのIL−2、1000〜3800pg/mLのIFN−γ、及び1000〜4300pg/mLのTNF−αへ処方するサイトカイン濃縮物を作製することを規定する、請求項7に記載の方法。
- 前記マイトジェン除去工程は、さらに、該誘導混合物を滅菌salineで洗浄し、MNCを回収し、そして、培養培地内に80μg/mLのシプロフロキサシンとともに再懸濁することを規定する、請求項1に記載の方法。
- 前記刺激工程は、さらに、該MNCの誘導混合物をフィトヘマグルチニン(PHA)及びシプロフロキサシンで刺激することを規定する、請求項1に記載の方法。
- 前記マイトジェン除去工程は、さらに、PHAのレベルを<150ng/mL以下まで除去することを規定する請求項11に記載の方法。
- 前記マイトジェン除去工程は、さらに、接線流モードでろ過することを規定する、請求項1に記載の方法。
- 前記インキュベーション工程は、さらに、24時間インキュベーションすることを規定する、請求項1に記載の方法。
- 前記清澄工程は、さらに、該誘導混合物を、0.45μmフィルタでろ過することを規定する、請求項1に記載の方法。
- 前記ウイルス除去工程は、さらに、4log10を超えるウイルスを除去することを規定する、請求項1に記載の方法。
- 前記ウイルス除去工程は、さらに、ヒト免疫不全ウイルス(HIV)、C型肝炎(HCV)、B型肝炎(HBV)、ヒトTリンパ球向性ウイルス(HTLV)、シミアンウイルス40(SV40)、ブタパルボウイルス(PPV)、仮性狂犬病ウイルス(PRV)、A型肝炎(HAV)、ウシウイルス性下痢症ウイルス(BVDV)、シンドビス、レオ及びアデノウイルスからなる群から選択されるウイルスを一掃することを規定する、請求項1に記載の方法。
- さらに、該一次細胞由来バイオロジック上澄を紫外線−C(UVC)にかけることにより、一次細胞由来バイオロジック上澄から偶発的な物質を一掃する工程を含む、請求項1に記載の方法。
- 前記UVCにかける工程は、さらに、一次細胞由来バイオロジック上澄をUVC放射源に沿って螺旋状に流すことによりUVCを一次細胞由来バイオロジックへ均一に送達することを規定する、請求項18に記載の方法。
- 前記均一に送達する工程は、さらに、波長254nmのUVCを一次細胞由来バイオロジックへ均一に送達することを規定する、請求項19に記載の方法。
- 前記均一に送達する工程は、さらに、最高150J/m2の線量のUVCを一次細胞由来バイオロジックへ送達することを規定する、請求項20に記載の方法。
- 自動細胞プロセッサに細胞を投入し、
細胞を自動で洗浄及び遠心分離し、そして、
精製された細胞を得る
工程を含む、細胞の自動化精製方法。 - さらに、精製される細胞をスケールアップ又はダウンするために細胞プロセッサの仕様を調整する工程を含む、請求項22に記載の方法。
- 前記投入工程は、さらに、白血球を自動細胞プロセッサ内のリンパ球分離培地(LSM)に投入することを規定する、請求項23に記載の方法。
- スケーラブルな細胞培養システム内で細胞を誘導し、そして、
細胞産物を作製する
工程を含む、細胞を誘導する方法。 - 前記作製工程は、さらに、IRX−2のサイトカインを作製することを規定する、請求項25に記載の方法。
- 前記サイトカインは、さらに、IL−1β、IL−2及びIFN−γを規定する、請求項26に記載の方法。
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US20070154399A1 (en) * | 2000-10-27 | 2007-07-05 | Hadden John W | Immunotherapy for immune suppressed patients |
EP2234642B8 (en) | 2007-11-28 | 2017-11-01 | IRX Therapeutics, Inc. | Method of increasing immunological effect |
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WO2006060779A2 (en) * | 2004-12-03 | 2006-06-08 | Case Western Reserve University | Novel methods, compositions and devices for inducing neovascularization |
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