JP2005179299A - 改変標的化t細胞の製造方法及び医薬 - Google Patents
改変標的化t細胞の製造方法及び医薬 Download PDFInfo
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- JP2005179299A JP2005179299A JP2003425009A JP2003425009A JP2005179299A JP 2005179299 A JP2005179299 A JP 2005179299A JP 2003425009 A JP2003425009 A JP 2003425009A JP 2003425009 A JP2003425009 A JP 2003425009A JP 2005179299 A JP2005179299 A JP 2005179299A
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Abstract
【解決手段】 非特異的に活性化した抗腫瘍活性をもつT細胞に、腫瘍特異的CTLのTCR遺伝子を導入することにより、抗腫瘍活性をもつ腫瘍特異的T細胞を製造し、少量の血液からでも腫瘍特異的な細胞免疫治療法を可能にする。この方法によりMHCクラスI拘束性の腫瘍特異的Th細胞が得られ、MHCクラスI分子を発現する腫瘍細胞に反応して抗腫瘍活性およびヘルパー活性を示す細胞を製造することができる。
【選択図】図3
Description
HLA−A24陽性健常人由来の腫瘍抗原WT1を有する腫瘍に特異的なCTLクローンTAK−1から、5’RACE法によりTCRα鎖遺伝子とTCRβ鎖遺伝子を単離し、配列を同定した。
あらかじめ、抗CD3抗体を培養プレートに固相化させた抗CD3抗体固相化プレートを準備しておき、末梢血から比重遠心法により回収した単核球を、100IU/mlのIL−2、50IU/mlのIL−12、10ng/mlのIFN−γ、2μg/mlの抗IL−4抗体(タイプ1サイトカイン)を加えたタイプ1培養条件で培養した。
タイプ1培養条件で2日間培養した単核球に、実施例1で得られたレンチウイルスベクターを含む培養上清とタイプ1サイトカインとを加えて培養し、さらにこの24時間後にもレンチウイルスベクターを含む培養上清とタイプ1サイトカインを加えて培養することにより、非特異的に活性化したT細胞にHLA−A24陽性健常人CTL由来のWT1特異的なTCRα鎖遺伝子とTCRβ鎖遺伝子を導入した。
ヒトのMHCクラスI抗原の中で日本人に最も高い頻度で存在するHLA−A24陽性の健常人の末梢血単核球をEBウイルスによりトランスフォームして得られたHLA−A24陽性リンフォブラスト細胞株(LCL)を仮想腫瘍細胞とし、WT1タンパク質のHLA−A24拘束性ペプチドを10μg/mlの濃度で添加し16時間反応(ペプチドをパルス)させた後、未反応のペプチドを洗浄した。この操作により細胞表面にHLA−A24/WT1ペプチド複合体が発現したLCL細胞が得られる。
Claims (17)
- 非特異的な抗腫瘍活性をもつTh細胞を誘導する工程と、そのTh細胞に抗原特異性を付与するための工程とを含むことを特徴とする、細胞治療用の細胞の製造方法。
- Th細胞に抗原特異性を付与するための工程が、癌関連抗原を認識するTCRの遺伝子を導入することにより行われる、請求項1記載の細胞治療用の細胞の製造方法。
- Th細胞に抗原特異性を付与するための工程が、癌関連抗原を認識するクラスI拘束性TCRの遺伝子を導入することにより行われる、請求項1記載の細胞治療用の細胞の製造方法。
- Th細胞に抗原特異性を付与するための工程が、癌関連抗原を認識するクラスII拘束性TCRの遺伝子を導入することにより行われる、請求項1記載の細胞治療用の細胞の製造方法。
- 癌関連抗原が、WT1、CEA、AFP、CA19−9、CA125、PSA、CA72−4、SCC、MK−1、MUC−1、p53、HER2、G250、gp−100、MAGE、BAGE、SART、MART、MYCN、BCR−ABL、TRP、LAGE、GAGEおよびNY−ESO1からなる群より選択される、請求項2−4のいずれかに記載の細胞治療用の細胞の製造方法。
- 非特異的な抗腫瘍活性をもつTh細胞を誘導する工程が、T細胞を含む材料を、抗CD3抗体およびIL−2の存在下で培養することにより行われる、請求項1記載の細胞治療用の細胞の製造方法。
- 抗原特異性を付与されたTh細胞を精製する工程をさらに含む、請求項1−6のいずれかに記載の細胞治療用の細胞の製造方法。
- 抗原特異性を付与されたTh細胞を精製する工程が、抗体磁気ビーズを使用することにより行われる、請求項7記載の細胞治療用の細胞の製造方法。
- 非特異的な抗腫瘍活性をもつTh1細胞とTc1細胞を誘導する工程と、そのTh1細胞とTc1細胞に抗原特異性を付与するための工程とを含むことを特徴とする、細胞治療用の細胞の製造方法。
- Th1細胞とTc1細胞に抗原特異性を付与するための工程が、癌関連抗原を認識するTCRの遺伝子を導入することにより行われる、請求項9記載の細胞治療用の細胞の製造方法。
- Th1細胞とTc1細胞に抗原特異性を付与するための工程が、癌関連抗原を認識するクラスI拘束性TCRの遺伝子を導入することにより行われる、請求項9記載の細胞治療用の細胞の製造方法。
- Th1細胞とTc1細胞に抗原特異性を付与するための工程が、癌関連抗原を認識するクラスII拘束性TCRの遺伝子を導入することにより行われる、請求項9記載の細胞治療用の細胞の製造方法。
- 癌関連抗原が、WT1、CEA、AFP、CA19−9、CA125、PSA、CA72−4、SCC、MK−1、MUC−1、p53、HER2、G250、gp−100、MAGE、BAGE、SART、MART、MYCN、BCR−ABL、TRP、LAGE、GAGEおよびNY−ESO1からなる群より選択される、請求項9−12のいずれかに記載の細胞治療用の細胞の製造方法。
- 非特異的な抗腫瘍活性をもつTh1細胞とTc1細胞を誘導する工程が、T細胞を含む材料を、抗CD3抗体、IL−2、およびIL−12の存在下で培養することにより行われる、請求項9記載の細胞治療用の細胞の製造方法。
- 抗原特異性を付与されたTh1細胞とTc1細胞とを分離する工程をさらに含む、請求項9−14のいずれかに記載の細胞治療用の細胞の製造方法。
- 抗原特異性を付与されたTh1細胞とTc1細胞とを分離する工程が、抗体磁気ビーズを使用することにより行われる、請求項15記載の細胞治療用の細胞の製造方法。
- 分離されたTh1細胞とTc1細胞を任意の割合で混合する工程をさらに含む、請求項15または16に記載の細胞治療用の細胞の製造方法。
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WO2008143255A1 (ja) * | 2007-05-22 | 2008-11-27 | Takara Bio Inc. | 細胞集団の製造方法 |
JP2013116891A (ja) * | 2011-11-01 | 2013-06-13 | Nagoya Univ | 髄膜腫治療用医薬組成物 |
US9670459B2 (en) | 2010-08-10 | 2017-06-06 | Takara Bio Inc. | Production method for cell populations |
WO2017159087A1 (ja) * | 2016-03-16 | 2017-09-21 | 国立大学法人京都大学 | 免疫細胞療法用ny-eso1抗原特異的t細胞の誘導方法 |
JP2018143247A (ja) * | 2012-09-12 | 2018-09-20 | 株式会社癌免疫研究所 | 抗原特異的ヘルパーt細胞レセプター遺伝子 |
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EP2087000A2 (en) * | 2006-09-29 | 2009-08-12 | Immunocore Ltd. | T cell therapies |
WO2008111506A1 (ja) * | 2007-03-09 | 2008-09-18 | Takara Bio Inc. | 遺伝子導入細胞調製方法 |
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US7655249B2 (en) * | 1998-09-30 | 2010-02-02 | Corixa Corporation | Compositions and methods for WT1 specific immunotherapy |
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Cited By (7)
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WO2008143255A1 (ja) * | 2007-05-22 | 2008-11-27 | Takara Bio Inc. | 細胞集団の製造方法 |
JPWO2008143255A1 (ja) * | 2007-05-22 | 2010-08-12 | タカラバイオ株式会社 | 細胞集団の製造方法 |
US9670459B2 (en) | 2010-08-10 | 2017-06-06 | Takara Bio Inc. | Production method for cell populations |
JP2013116891A (ja) * | 2011-11-01 | 2013-06-13 | Nagoya Univ | 髄膜腫治療用医薬組成物 |
JP2018143247A (ja) * | 2012-09-12 | 2018-09-20 | 株式会社癌免疫研究所 | 抗原特異的ヘルパーt細胞レセプター遺伝子 |
US11091531B2 (en) | 2012-09-12 | 2021-08-17 | International Institute Of Cancer Immunology, Inc. | Antigen-specific helper T-cell receptor genes |
WO2017159087A1 (ja) * | 2016-03-16 | 2017-09-21 | 国立大学法人京都大学 | 免疫細胞療法用ny-eso1抗原特異的t細胞の誘導方法 |
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