JP2022525763A - 組換えerIL-15 NK細胞 - Google Patents
組換えerIL-15 NK細胞 Download PDFInfo
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Abstract
Description
サイズが8kbで、2020年2月19日に作成され、本出願と共にEFS-Webを介して電子出願されたSequence_listing_ST25という名称の配列表のASCIIテキストファイルの内容は、その全体が参照によって援用される。
KpnI/NotI制限酵素部位が側面に位置する3つのgBlockを、Integrated DNA Technologiesで合成し、同様に消化したpNEUkv1-CD16-erIL2プラスミド骨格の中に、それぞれの配列をサブクローニングするために使用し、以下のプラスミドを作り出した。
pNEUkv1-CD16(158V)-IRES-(KpnI)-[IL-15 LSP]-(NotI)
pNEUkv1-CD16(158V)-IRES--(KpnI)-[erIL-15 LSP]-(NotI)
pNEUkv1-CD16(158V)-IRES--(KpnI)-[IL-15 SSP]-(NotI)
Claims (25)
- erLSP-IL-15をコードする第1のセグメントを含む組換え核酸を含む、遺伝子改変NK細胞。
- 前記NK細胞がNK-92細胞である、請求項1に記載の遺伝子改変NK細胞。
- 前記組換え核酸がDNAである、請求項1又は2に記載の遺伝子改変NK細胞。
- 前記組換え核酸が線状プラスミドである、請求項1~3のいずれか一項に記載の遺伝子改変NK細胞。
- 前記組換え核酸が、CD16又は高親和性CD16をコードする第2のセグメントをさらに含む、請求項1~4のいずれか一項に記載の遺伝子改変NK細胞。
- 前記組換え核酸が、キメラ抗原受容体をコードする第3のセグメントをさらに含む、請求項1~5のいずれか一項に記載の遺伝子改変NK細胞。
- 前記組換え核酸が、免疫刺激をもたらす、チェックポイント阻害を妨げるタンパク質、免疫抑制に関与するサイトカインに結合する/サイトカインを阻害するタンパク質、及び/又はIL-15受容体アルファ鎖をコードする第4のセグメントをさらに含む、請求項1~6のいずれか一項に記載の遺伝子改変NK細胞。
- 前記組換え核酸が、(a)前記改変されたNK細胞を外来性サイトカインから独立させるのに、及び(b)前記改変されたNK細胞の近くの他の免疫コンピテント細胞の刺激/活性化を可能にするのに十分な量で、erLSP-IL-15の発現を引き起こすのに十分な強度を有するプロモーターを含む、請求項1~7のいずれか一項に記載の遺伝子改変NK細胞。
- 前記erLSP-IL-15におけるIL-15部分が、コドン最適化ヒトIL-15配列を含む、請求項1~8のいずれか一項に記載の遺伝子改変NK細胞。
- CD16を介して前記細胞につながれた抗体をさらに含む、請求項1~9のいずれか一項に記載の遺伝子改変NK細胞。
- NK細胞を改変するための方法であって、
前記細胞に組換え核酸を導入することを含み、前記組換え核酸は、erLSP-IL-15をコードする第1のセグメントを含む、方法。 - 前記NK細胞がNK-92細胞である、請求項11に記載の方法。
- 前記組換え核酸がDNAである、請求項11又は12に記載の方法。
- 前記組換え核酸が線状プラスミドである、請求項11~13のいずれか一項に記載の方法。
- 前記組換え核酸が、CD16又は高親和性CD16をコードする第2のセグメントをさらに含む、請求項11~14のいずれか一項に記載の方法。
- 前記組換え核酸が、キメラ抗原受容体をコードする第3のセグメントをさらに含む、請求項11~15のいずれか一項に記載の方法。
- 前記組換え核酸が、免疫刺激をもたらす、チェックポイント阻害を妨げるタンパク質、免疫抑制に関与するサイトカインに結合する/サイトカインを阻害するタンパク質、及び/又はIL-15受容体アルファ鎖をコードする第4のセグメントをさらに含む、請求項11~16のいずれか一項に記載の方法。
- 前記組換え核酸が、(a)前記改変されたNK細胞を外来性サイトカインから独立させるのに、及び(b)前記改変されたNK細胞の近くの他の免疫コンピテント細胞の刺激/活性化を可能にするのに十分な量で、erLSP-IL-15の発現を引き起こすのに十分な強度を有するプロモーターを含む、請求項11~17のいずれか一項に記載の方法。
- 前記erLSP-IL-15におけるIL-15部分が、コドン最適化ヒトIL-15配列を含む、請求項11~18のいずれか一項に記載の方法。
- CD16を介して前記細胞につながれた抗体をさらに含む、請求項11~19のいずれか一項に記載の方法。
- 請求項1~10のいずれか一項に記載の遺伝子改変NK細胞と組み合わせた薬学的に許容され得るキャリアを含む医薬組成物。
- 患者への注入のために製剤化された、請求項21に記載の医薬組成物。
- 投与単位当たり少なくとも1×109細胞を含む、請求項21に記載の医薬組成物。
- 癌の治療における、請求項1~10のいずれか一項に記載の遺伝子改変されたNK細胞の使用。
- 前記治療が、TMEに侵入する薬物の投与、免疫抑制を低下させる薬物の投与、免疫コンピテント細胞を刺激する薬物の投与、癌ワクチン組成物の投与、及び/又は免疫応答の維持を助け且つ記憶細胞の発達を促進する薬物の投与をさらに含む、請求項24に記載の使用。
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WO2018165291A1 (en) * | 2017-03-08 | 2018-09-13 | Nantkwest, Inc. | MODIFIED NK-92 haNK003 CELLS FOR THE CLINIC |
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AU2013203171B2 (en) | 2006-01-13 | 2016-05-19 | The Government of the United States, as represented by The Secretary, Department of Health and Human Services, National Institutes of Health | Codon optimized IL-15 and IL-15R-alpha genes for expression in mammalian cells |
WO2012136231A1 (en) | 2010-09-08 | 2012-10-11 | Chemotherapeutisches Forschungsinstitut Georg-Speyer-Haus | Interleukin 15 as selectable marker for gene transfer in lymphocytes |
ES2795023T3 (es) | 2011-09-16 | 2020-11-20 | Baylor College Medicine | Reconocimiento específico del microambiente tumoral mediante el uso de células NKT manipuladas |
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WO2016126608A1 (en) * | 2015-02-02 | 2016-08-11 | Novartis Ag | Car-expressing cells against multiple tumor antigens and uses thereof |
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