JP2021512965A - Treg細胞を標的とするための方法及び組成物 - Google Patents
Treg細胞を標的とするための方法及び組成物 Download PDFInfo
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Abstract
【選択図】なし
Description
本出願は、2018年2月13日に出願された米国仮特許出願第62/630,084号への優先権を主張するものであり、参照によりその全体が本明細書に組み込まれる。
本出願は、その開示の一部として、2019年2月13日に作成された32,546バイトのサイズをもつ「43282o4613.txt」という名前のファイル内の生物学的配列表を含み、参照によりその全体が本明細書に組み込まれる。
別途定義されない限り、本明細書で用いるすべての技術的及び科学的用語は、本発明が属する技術分野の当業者によって一般的に理解されるものと同じ意味を表す。本明細書に記載されるものと同様または同等の方法及び材料は、本発明または本発明の試験で使用され得るが、適切な方法及び材料が本明細書に記載される。材料、方法、及び実施例は単なる例示であり、限定することを意図するものではない。
NEO−201は、機能的なTreg細胞を単離することができる。
NEO−201は、補体依存性細胞毒性(CDC)によってTregを死滅させることができる。
ヒト化NEO−201モノクローナル抗体の作製
筋萎縮性側索硬化症(ALS)、抗体依存性細胞毒性(ADCC)、時間0から無限大までの血漿濃度−時間曲線下面積(AUCinf)、時間0から無限までの血漿濃度−時間曲線下用量正規化面積(AUCinf/D)、ベースライン(BL)、補体依存性細胞毒性(CDC)、クリアランス(CL)、最大観測血漿濃度(Cmax)、用量で正規化した測定最大血漿濃度(Cmax/D)、エストロゲン受容体(ER)、半減期(HL)、免疫組織化学(IHC)、多発性硬化症(MS)ナチュラルキラー(NK)、非小細胞肺癌(NSCLC)、末梢血単核細胞(PBMC)、プロゲステロン受容体(PR)、腫瘍関連抗原(TAA)、最大観察血漿中濃度の時間(Tmax)、分布体積(Vz)。
以下の表の各文書を含む、本明細書で引用される各文書は、参照によりその全体が本明細書に組み込まれる。
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Claims (40)
- インビボでTreg細胞を死滅させる方法であって、有効量のNEO−201抗体を患者に投与することを含む、前記方法。
- 患者における抗がん免疫応答を増強する方法であって、有効量のNEO−201抗体を前記患者に投与することを含む、前記方法。
- がんワクチンを前記患者に投与することをさらに含む、請求項2に記載の方法。
- 患者におけるがんのTreg細胞浸潤を減少させる方法であって、有効量のNEO−201抗体を前記患者に投与することを含む、前記方法。
- 前記がんが、CEACAM5またはCEACAM6を発現しない、請求項2〜4のいずれか1項に記載の方法。
- 前記投与前または投与時に、前記がんが、CEACAM5及びCEACAM6陰性であると決定することをさらに含む、請求項3〜5のいずれか1項に記載の方法。
- がんを治療または予防する、がんの負荷を軽減する、またはがんの成長もしくは増殖速度を低下させる方法であって、有効量のNEO−201抗体を、それを必要とする患者に投与することを含み、前記がんが、CEACAM5及びCEACAM6陰性である、前記方法。
- 別の治療剤を前記患者に投与することをさらに含む、請求項7に記載の方法。
- 前記他の薬剤が、(a)微小管阻害剤、トポイソメラーゼ阻害剤、プラチン、アルキル化剤、及び代謝拮抗剤、(b)MK−2206、ON 013105、RTA 402、BI 2536、ソラフェニブ、ISIS−STAT3Rx、微小管阻害剤、トポイソメラーゼ阻害剤、プラチン、アルキル化剤、代謝拮抗剤、パクリタキセル、ゲムシタビン、ドキソルビシン、ビンブラスチン、エトポシド、5−フルオロウラシル、カルボプラチン、アルトレタミン、アミノグルテチミド、アムサクリン、アナストロゾール、アザシチジン、ブレオマイシン、ブスルファン、カルムスチン、クロラムブシル、2−クロロデオキシアデノシン、シスプラチン、コルヒチン、シクロホスファミド、シタラビン、シトキサン、ダカルバジン、ダクチノマイシン、ダウノルビシン、ドセタキセル、リン酸エストラムスチン、フロクスウリジン、フルダラビン、ゲンツズマブ、ヘキサメチルメラミン、ヒドロキシ尿素、イフォスファミド、イマチニブ、インターフェロン、イリノテカン、ロムスチン、メクロレタミン、メルファレン、6−メルカプトプリン、メトトレキサート、マイトマイシン、ミトタン、ミトキサントロン、ペントスタチン、プロカルバジン、リツキシマブ、ストレプトゾシン、タモキシフェン、テモゾロミド、テニポシド、6−チオグアニン、トポテカン、トラスツズマブ、ビンクリスチン、ビンデシン、及び/またはビノレルビン、(c)1−D−リボフラノシル−1,2,4−トリアゾール−3カルボキサミド、9−>2−ヒドロキシ−エトキシメチルグアニン、アダマンタンアミン、5−ヨード−2’−デオキシウリジン、トリフルオロチミジン、インターフェロン、アデニンアラビノシド、プロテアーゼ阻害剤、チミジンキナーゼ阻害剤、糖または糖タンパク質合成阻害剤、構造タンパク質合成阻害剤、付着及び吸着阻害剤、ならびにアシクロビル、ペンシクロビル、バラシクロビル、及びガンシクロビルなどのヌクレオシド類似体、(d)PD−1阻害剤、またはKEYTRUDA(登録商標)(ペンブロリズマブ)もしくはOPDIVO(登録商標)(ニボルマブ)などの抗PD−1抗体、あるいは(e)CTLA−4阻害剤、またはYLERVOY(登録商標)イピリムマブなどの抗CTLA−4抗体、から選択される、請求項8に記載の方法。
- 前記NEO−201抗体が、前記患者における抗がん免疫応答を誘発または増大させる、請求項7〜9のいずれか1項に記載の方法。
- インビトロでTreg細胞を死滅させる方法であって、前記Treg細胞をNEO−201抗体と接触させることを含む、前記方法。
- 前記Treg細胞を補体と接触させることをさらに含む、請求項11に記載の方法。
- 前記Treg細胞が、CDCによって死滅する、請求項11または12に記載の方法。
- 前記Treg細胞をエフェクター細胞と接触させることをさらに含む、請求項11に記載の方法。
- 前記エフェクター細胞が、ナチュラルキラー細胞を含む、請求項14に記載の方法。
- 前記Treg細胞が、ADCCによって死滅する、請求項11、14、または15に記載の方法。
- 前記NEO−201抗体が、細胞毒性部分に結合されている、先行請求項のいずれか1項に記載の方法。
- Treg細胞を検出する方法であって、前記Treg細胞による前記NEO−201抗原の発現を検出することを含み、任意に、血液または生検サンプルなどの患者サンプル中のTreg細胞のレベルが、がんを診断するまたはがんの進行を決定するために使用される、前記方法。
- 前記Treg細胞をNEO−201抗体と接触させることを含み、任意に、前記NEO−201抗体が、標識に直接的または間接的に結合される、請求項18に記載の方法。
- 前記検出が、細胞選別、任意に、蛍光活性化細胞選別を含む、請求項18または19に記載の方法。
- Treg細胞を染色する方法であって、細胞をNEO−201抗体と接触させることを含む、前記方法。
- 前記NEO−201抗体が、標識に直接的または間接的に結合される、請求項21に記載の方法。
- Treg細胞を単離する方法であって、前記NEO−201抗原を発現する細胞を単離することを含む、前記方法。
- Treg細胞を含有するサンプルをNEO−201抗体と接触させることを含み、任意に、前記NEO−201抗体が、直接的または間接的に標識される、請求項23に記載の方法。
- 前記サンプルが、血液または骨髄であるか、またはそれを含む、請求項24に記載の方法。
- NEO−201陽性Treg細胞をNEO−201陰性細胞から分離することを含む、請求項23〜25のいずれか1項に記載の方法。
- 前記Treg細胞が、細胞選別、任意に、蛍光活性化細胞選別によって単離される、請求項23〜26のいずれか1項に記載の方法。
- 前記Treg細胞が、サンプルを、NEO−201抗体を含む支持体と接触させることによって単離され、それにより前記Treg細胞が、前記支持体上に保持される、請求項23〜26のいずれか1項に記載の方法。
- 前記NEO−201抗体が、配列番号28及び配列番号29に含まれるCDR配列の少なくとも1つ、2つ、3つ、4つ、5つ、または6つすべてを含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体が、配列番号38に対して少なくとも90%の同一性を有する可変重鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体が、配列番号39に対して少なくとも90%の同一性を有する可変軽鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体が、配列番号38に対して少なくとも90%の同一性を有する可変重鎖配列及び配列番号39に対して少なくとも90%の同一性を有する可変軽鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体が、配列番号28のアミノ酸20〜470に対して少なくとも90%の同一性を有する重鎖配列及び配列番号29のアミノ酸20〜233に対して少なくとも90%の同一性を有する軽鎖配列を含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体が、配列番号28及び配列番号29に含まれるCDR配列の6つすべてを含む、請求項32または33に記載の方法。
- 前記NEO−201抗体が、ヒトIgG1定常ドメインを含む、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体が、ヒト化されている、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体が、別の部分にコンジュゲートされている、先行請求項のいずれか1項に記載の方法。
- 前記NEO−201抗体が、別の細胞毒性部分、標識、放射性部分、または親和性タグにコンジュゲートされている、先行請求項のいずれか1項に記載の方法。
- 前記がんが、血液学的悪性腫瘍、非小細胞肺癌などの肺癌、黒色腫、胃腸癌、卵巣癌、頭頸部の扁平上皮癌、肝細胞癌、乳癌、膵臓癌、中皮腫、転移性腎細胞癌、及び前立腺癌から選択される、請求項1〜10のいずれか1項に記載の方法。
- 前記Treg細胞を遺伝子改変することと、任意に、前記細胞を前記患者または別の個体に導入することと、をさらに含む、請求項23〜28のいずれか1項に記載の方法。
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WO2019160970A1 (en) | 2019-08-22 |
BR112020016374A2 (pt) | 2020-12-15 |
CN112041343A (zh) | 2020-12-04 |
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