JP2023519727A - Cd3融合タンパク質およびその使用 - Google Patents
Cd3融合タンパク質およびその使用 Download PDFInfo
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- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
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Abstract
Description
- CD3ε外部ドメイン、
- CD3δ外部ドメインまたはCD3γ外部ドメイン、
- 膜貫通ドメイン、および
- CD3ζドメイン
を含むCD3融合タンパク質を提供する。
- CD8シグナルペプチドドメイン、
- CD3δ外部ドメインおよびCD3ε外部ドメイン、
- CD8ヒンジドメイン、
- CD28膜貫通ドメイン、
- CD3ζドメイン
を含む。
- 本明細書に記載されるCD3融合タンパク質を発現させるステップ、
- T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
を含む、方法に言及する。
- 本明細書に記載されるCD3融合タンパク質を発現させるステップ、
- 内因性TCRを欠失させるステップ、
- T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
を含んでもよい。
- CD3ε外部ドメイン、
- CD3δ外部ドメインまたはCD3γ外部ドメイン、
- 膜貫通ドメイン、および
- CD3ζドメイン
を含むCD3融合タンパク質を提供する。
- CD8シグナルペプチドドメイン、
- CD3δ外部ドメインおよびCD3ε外部ドメイン、
- CD8ヒンジドメイン、
- CD28膜貫通ドメイン、
- CD3ζドメイン
を含む。
- 本明細書に記載されるCD3融合タンパク質をT細胞において発現させるステップ、
- T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
を含む、方法に言及する。
- 本明細書に記載されるCD3融合タンパク質をT細胞において発現させるステップ、
- T細胞の内因性TCRを欠失させるステップ、
- T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
を含んでもよい。
- 本明細書に記載されるCD3融合タンパク質をT細胞において発現させるステップ、
- T細胞の内因性TCRを欠失させるステップ、
- T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
- 外因性T細胞エフェクター分子を発現させるステップ
- 任意選択で、CD3融合タンパク質を欠失させるステップ
を含む。
TCRなどのヘテロ二量体細胞表面タンパク質についての効率的なノックアウト戦略の作成が、レシピエント細胞の作製のために重要であることは当業者には明らかである。
(a)内因性TCRα鎖のノックアウト、
(b)機能的TCRを欠いている細胞についての選択、
(c)内因性TCRβ鎖のノックアウト、
(d)TCRα鎖の一過性発現、
(e)機能的TCRを欠いている細胞についての選択
によって達成され得るか、または代わりに、以下のステップ:
(a)内因性TCRβ鎖のノックアウト、
(b)機能的TCRを欠いている細胞についての選択、
(c)内因性TCRα鎖のノックアウト、
(d)TCRβ鎖の一過性発現、
(e)機能的TCRを欠いている細胞についての選択
によって達成される。
(a)内因性TCRβ鎖のノックアウト、
(b)機能的TCRを欠いている細胞についての選択、
(c)内因性TCRα鎖のノックアウト、
(d)TCRβ鎖の一過性発現、
(e)機能的TCRを欠いている細胞についての選択
によって達成され得る。
項目1. - CD3ε外部ドメイン、
- CD3δ外部ドメインまたはCD3γ外部ドメイン、
- 膜貫通ドメイン、および
- CD3ζドメイン
を含むCD3融合タンパク質。
- CD8シグナルペプチドドメイン、
- CD3δ外部ドメインおよびCD3ε外部ドメイン、
- CD8ヒンジドメイン、
- CD28膜貫通ドメイン、
- CD3ζドメイン
を含む、先行する項目に記載のCD3融合タンパク質。
- 項目1~32に記載の融合タンパク質を発現させるステップ、
- T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
を含む、方法。
- TCRを欠失させるステップ、
- T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
を含む、項目39に記載の方法。
Claims (16)
- - CD3ε外部ドメイン、
- CD3δ外部ドメインまたはCD3γ外部ドメイン、
- 膜貫通ドメイン、および
- CD3ζドメイン
を含むCD3融合タンパク質。 - 前記融合タンパク質が、
- CD8シグナルペプチドドメイン、
- CD3δ外部ドメインおよびCD3ε外部ドメインを含むCD3ヘテロ二量体、
- CD8ヒンジドメイン、
- CD28膜貫通ドメイン、
- CD3ζドメイン
を含む、先行する請求項に記載のCD3融合タンパク質。 - 前記CD3δ外部ドメインが、配列番号2であるアミノ酸配列を含み、前記CD3ε外部ドメインが、配列番号4であるアミノ酸配列を含み、前記CD3ζドメインが、配列番号8であるアミノ酸配列を含む、先行する請求項に記載のCD3融合タンパク質。
- 請求項1~3に記載の融合タンパク質をコードする配列を含有する核酸分子。
- T細胞のTCR非依存性活性化のための方法であって、
- 請求項1~3に記載の融合タンパク質を前記T細胞において発現させるステップ、
- 前記T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
を含む、方法。 - - 請求項1~3に記載の融合タンパク質を前記T細胞において発現させるステップ、
- 前記T細胞の内因性TCRを欠失させるステップ、
- 前記T細胞をCD3刺激剤およびCD28刺激剤で刺激するステップ
を含む、請求項6に記載の方法。 - 前記CD3刺激剤が、活性化抗CD3抗体またはその結合性断片である、請求項5または6に記載の方法。
- 前記CD28刺激剤が、活性化抗CD28抗体またはその結合性断片である、請求項5または6に記載の方法。
- 前記CD3刺激剤および前記CD28刺激剤が、抗CD3抗体および抗CD28抗体またはその結合性断片を含む組成物である、請求項5または6に記載の方法。
- 抗CD3抗体および抗CD28抗体またはその結合性断片を含む前記組成物が、固定化されている、請求項9に記載の方法。
- 抗CD3抗体および抗CD28抗体またはその結合性断片を含む前記組成物が、ビーズ上に固定化されている、請求項10に記載の方法。
- 請求項1~3に記載の融合タンパク質を含むT細胞。
- 前記T細胞が、内因性TCRを欠いている、請求項12に記載のT細胞。
- 医薬としての使用のための、請求項12および13のいずれか一項に記載のT細胞。
- がんまたはウイルス性疾患の処置における使用のための、請求項12および13のいずれか一項に記載のT細胞。
- 外因性エフェクター分子の試験および特性評価のための、請求項12および13に記載のT細胞の使用。
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