JP7411578B2 - 癌を治療するための物質及び方法 - Google Patents
癌を治療するための物質及び方法 Download PDFInfo
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Description
本出願は、2018年6月1日出願の米国特許出願第62/679、348号、及び、2018年10月31日出願の米国特許出願第62/753、485号に基づく優先権を主張するものである。上記出願の開示内容は、本開示の一部と見なされる(参照により本明細書に援用される)。
本開示は、癌の治療に関与する方法及び物質(薬剤)に関する。例えば、本開示は、癌を有する哺乳動物(例えば、ヒト)を治療するための養子細胞療法(例えば、キメラ抗原受容体T細胞療法)において、1以上のサイトカイン(例えば、GM-CSF)の発現レベルを低下させたキメラ抗原受容体T細胞を使用するための方法及び物質を提供する。
例えば、GM-CSFポリペプチドの発現レベルを低下させたT細胞を哺乳動物に投与しても、CRSに関連するサイトカイン(例えば、CRSクリティカルサイトカイン)の放出は生じない。CRSに関連するサイトカインの例としては、これに限定しないが、IL-6、G-CSF、IFN-g、IL-1B、IL-10、MCP-1、MIG、MIP、MIP-1b、TNF-a、IL-2、及びパーフォリンが挙げられる。
Claims (24)
- 顆粒球マクロファージコロニー刺激因子(GM-CSF)ポリペプチドの発現レベルを低下させたキメラ抗原受容体T細胞を作製する方法であって、
核酸構築物であって、(a)GM-CSFメッセンジャーRNAに対して相補的なガイドRNAをコードする核酸と、(b)Casヌクレアーゼをコードする核酸と、(c)キメラ抗原受容体をコードする核酸とを含む、該核酸構築物を、生体外T細胞に導入する導入ステップを含み、
前記キメラ抗原受容体をコードする前記核酸が、配列番号2に記載の核酸配列を含むことを特徴とする方法。 - 請求項1に記載の方法であって、
前記ガイドRNAが、配列番号1に記載の核酸配列を含むことを特徴とする方法。 - 請求項1または2に記載の方法であって、
前記Casヌクレアーゼが、Cas9ヌクレアーゼであることを特徴とする方法。 - 請求項1~3のいずれかに記載の方法であって、
前記核酸構築物が、ウイルスベクターであることを特徴とする方法。 - 請求項4に記載の方法であって、
前記ウイルスベクターが、レンチウイルスベクターであることを特徴とする方法。 - 請求項1~5のいずれかに記載の方法であって、
前記キメラ抗原受容体が、腫瘍関連抗原を標的とすることを特徴とする方法。 - 請求項6に記載の方法であって、
前記腫瘍関連抗原が、CD19であることを特徴とする方法。 - 請求項1~7のいずれかに記載の方法であって、
前記導入ステップが、形質導入を含むことを特徴とする方法。 - 顆粒球マクロファージコロニー刺激因子(GM-CSF)ポリペプチドの発現レベルを低下させたキメラ抗原受容体T細胞を作製する方法であって、
複合体であって、(a)GM-CSFメッセンジャーRNAに対して相補的なガイドRNAと、(b)Casヌクレアーゼとを含む、該複合体を、生体外T細胞に導入する第1の導入ステップと、
キメラ抗原受容体をコードする核酸を前記生体外T細胞に導入する第2の導入ステップと、
を含み、
前記キメラ抗原受容体をコードする前記核酸が、配列番号2に記載の核酸配列を含むことを特徴とする方法。 - 請求項9に記載の方法であって、
前記ガイドRNAが、配列番号1に記載の核酸配列を含むことを特徴とする方法。 - 請求項9または10に記載の方法であって、
前記Casヌクレアーゼが、Cas9ヌクレアーゼであることを特徴とする方法 - 請求項9~11のいずれかに記載の方法であって、
前記複合体が、リボ核タンパク質であることを特徴とする方法。 - 請求項9~12のいずれかに記載の方法であって、
前記キメラ抗原受容体が、腫瘍関連抗原を標的とすることを特徴とする方法。 - 請求項13に記載の方法であって、
前記腫瘍関連抗原が、CD19であることを特徴とする方法。 - 請求項9~14のいずれかに記載の方法であって、
前記第1の導入ステップ及び前記第2の導入ステップが、エレクトロポレーションを含むことを特徴とする方法。 - 哺乳動物の癌の治療に使用するための医薬組成物であって、
顆粒球マクロファージコロニー刺激因子(GM-CSF)ポリペプチドの発現レベルを低下させたキメラ抗原受容体T細胞を含み、
前記キメラ抗原受容体T細胞に導入されているキメラ抗原受容体が、配列番号2に記載の核酸配列を含む核酸によってコードされることを特徴とする医薬組成物。 - 請求項16に記載の医薬組成物であって、
前記哺乳動物が、ヒトであることを特徴とする医薬組成物。 - 請求項16または17に記載の医薬組成物であって、
前記癌が、リンパ腫または白血病であることを特徴とする医薬組成物。 - 請求項18に記載の医薬組成物であって、
前記リンパ腫が、びまん性大細胞型B細胞リンパ腫であることを特徴とする医薬組成物。 - 請求項18に記載の医薬組成物であって、
前記白血病が、急性リンパ芽球性白血病であることを特徴とする医薬組成物。 - 請求項16~20のいずれかに記載の医薬組成物であって、
前記キメラ抗原受容体が、腫瘍関連抗原を標的とすることを特徴とする医薬組成物。 - 請求項21に記載の医薬組成物であって、
前記腫瘍関連抗原が、CD19であることを特徴とする医薬組成物。 - キメラ抗原受容体T細胞のT細胞エフェクター機能を改善する方法であって、
核酸構築物であって、(a)GM-CSFメッセンジャーRNAに対して相補的なガイドRNAをコードする核酸と、(b)Casヌクレアーゼをコードする核酸と、(c)キメラ抗原受容体をコードする核酸とを含む、該核酸構築物を、生体外T細胞に導入する導入ステップを含み、
前記キメラ抗原受容体をコードする前記核酸が、配列番号2に記載の核酸配列を含むことを特徴とする方法。 - キメラ抗原受容体T細胞のT細胞エフェクター機能を改善する方法であって、
複合体であって、(a)GM-CSFメッセンジャーRNAに対して相補的なガイドRNAと、(b)Casヌクレアーゼとを含む、該複合体を、生体外T細胞に導入する第1の導入ステップと、
キメラ抗原受容体をコードする核酸を前記生体外T細胞に導入する第2の導入ステップと、を含み、
前記キメラ抗原受容体をコードする前記核酸が、配列番号2に記載の核酸配列を含むことを特徴とする方法。
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EP3801563A1 (en) | 2021-04-14 |
EP3801563A4 (en) | 2022-05-11 |
JP2021525519A (ja) | 2021-09-27 |
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