JP4457169B2 - 非機能性p2x7レセプター抗体、癌及びその他の容態の診断及び処理 - Google Patents
非機能性p2x7レセプター抗体、癌及びその他の容態の診断及び処理 Download PDFInfo
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Description
ことができる。
本明細書では、動物において特異的非機能性P2X7抗体を使い、ヒト及び他の哺乳動物でのほとんどの癌を診断するために本発明のプローブ及び方法の一般的な適用を実証するという例示により説明がなされている。
アポトーシスを起こそうと企てている癌細胞の細胞表面上で発現される、この明らかに偏在するP2X7非機能性レセプターを、ヒト及び他の動物のほとんどの癌の処置に使うことができる。以下に例示がある。
非機能性P2X7へのアフィニティー精製抗体の存在下及び不在下の両方で、マクロファージベース上にマウスハイブリドーマ細胞を増殖した。4日間を超えたとき、精製された正常IgGのみが存在する中で増殖した細胞数は1〜7×104である一方で、非機能性P2X7抗体の存在下では、細胞数はほんの1.5×104であった。
特異的なアフィニティー精製抗体(特異性を大きく改善するためのもの)を、7日間にわたって液体中で、又はジメチコン・クリーム基剤に懸濁してのいずれかで、3つのヒト基底細胞癌(「BCC」)に適用した。コントロール皮膚は、タンパク質標的の不在により、全体的に影響を受けなかった一方で、処置後にBCC病変の痕跡は検出されなかった。
治療学的目的に能動的免疫化もまた使うことができる。この場合には、ヒト又は他の哺乳動物は、細胞表面で非機能的(ATPが減少した)形状にあるレセプターによってのみ適合されるコンフォメーションを模倣したコンフォメーションにある特異的エピトープ(単数)又はエピトープ(複数)に対して免疫化される必要がある。機能性レセプターに存在するエピトープの形状の部分的な暴露を含むコンフォメーションの柔軟性は避けられるべきである。例としてのエピトープGly200−Thr215のシスコンフォメーションは、適切な手段で使われる前に固定されるべきである。この概念が堅実であることについての追加証拠としては、抗体を造るために使われたマウス、ウサギ及びヒツジを含む数々の動物の免疫力が低下していないという観察がある。これらの多くの動物では、これまで腫瘍の成長はない。
本発明は、その全ての面において、疾患の早期且つ正確な診断及び効果的な処置(多くの場合には、従来技術で利用可能なものに比べて、はるかに侵襲性又は外傷性でない)をすることができる可能性とともに、ヒト及び動物の医学及び健康の分野に適用を有する。
Claims (15)
- ヒトP2X7レセプターの細胞外ドメインに結合する抗体を作製するためのエピトープペプチドであって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合せず、前記エピトープペプチドが、シスコンフォメーションであるPro210含むヒトP2X7レセプターのアミノ酸断片を含む、エピトープペプチド。
- 前記ヒトP2X7レセプターのアミノ酸断片が、Gly200からThr215までのアミノ酸配列を有する、請求項1に記載のエピトープペプチド。
- シスコンフォメーションであるPro210を含む、単離されたヒトP2X7レセプター。
- 疾患又は容態の検出用のヒトP2X7レセプターの細胞外ドメインに結合する抗体であって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合しない、抗体の使用。
- 新形成前組織の検出用の薬剤の製造のための、ヒトP2X7レセプターの細胞外ドメインに結合する抗体の使用であって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合しない、抗体の使用。
- 上皮系細胞癌の検出用の薬剤の製造のための、ヒトP2X7レセプターの細胞外ドメインに結合する抗体の使用であって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合しない、抗体の使用。
- 上皮系細胞癌が、前立腺癌、乳癌、皮膚癌、肺癌、頚癌、子宮癌、胃癌、食道癌、膀胱癌、大腸癌及び膣癌から成る群より選択される、請求項6に記載の使用。
- 血液癌の検出用の薬剤の製造のための、ヒトP2X7レセプターの細胞外ドメインに結合する抗体の使用であって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合しない、抗体の使用。
- 血液癌が、悪性リンパ腫である、請求項8に記載の使用。
- 疾患又は容態の治療用又は予防用の、ヒトP2X7レセプターの細胞外ドメインに結合する抗体であって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合しない、抗体の使用。
- 新形成前組織の治療用又は予防用の薬剤の製造のための、ヒトP2X7レセプターの細胞外ドメインに結合する抗体であって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合しない、抗体の使用。
- 上皮系細胞癌の治療用又は予防用の薬剤の製造のための、ヒトP2X7レセプターの細胞外ドメインに結合する抗体であって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合しない、抗体の使用。
- 上皮系細胞癌が、前立腺癌、乳癌、皮膚癌、肺癌、頚癌、子宮癌、胃癌、食道癌、膀胱癌、大腸癌及び膣癌から成る群より選択される、請求項12に記載の使用。
- 血液癌の治療用又は予防用の薬剤の製造のための、ヒトP2X7レセプターの細胞外ドメインに結合する抗体であって、前記ヒトP2X7レセプターのアミノ酸210にあるプロリンがシスコンフォメーションであり、該抗体が、アミノ酸210にあるプロリンがトランスコンフォメーションであるヒトP2X7レセプターの細胞外ドメインに結合しない、抗体の使用。
- 血液癌が、悪性リンパ腫である、請求項14に記載の使用。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
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AUPR2579A AUPR257901A0 (en) | 2001-01-17 | 2001-01-17 | Diagnosis and treatment of malignant lymphoma |
AUPR5890A AUPR589001A0 (en) | 2001-06-22 | 2001-06-22 | An antibody cancer therapeutic |
AUPR5891A AUPR589101A0 (en) | 2001-06-22 | 2001-06-22 | Diagnosis of cell cancers using an antibody to non-functionalP2X, receptors |
AUPR7431A AUPR743101A0 (en) | 2001-09-03 | 2001-09-03 | A cancer therapeutic |
AUPR7430A AUPR743001A0 (en) | 2001-09-03 | 2001-09-03 | Diagnosis and treatment of irritable bowel syndrome |
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JP2002558379A Division JP4384852B2 (ja) | 2001-01-17 | 2002-01-17 | 非機能性p2x7レセプター抗体、癌及びその他の容態の診断及び処置 |
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JP2009235074A JP2009235074A (ja) | 2009-10-15 |
JP4457169B2 true JP4457169B2 (ja) | 2010-04-28 |
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JP2002558379A Expired - Fee Related JP4384852B2 (ja) | 2001-01-17 | 2002-01-17 | 非機能性p2x7レセプター抗体、癌及びその他の容態の診断及び処置 |
JP2009112881A Expired - Lifetime JP4457169B2 (ja) | 2001-01-17 | 2009-05-07 | 非機能性p2x7レセプター抗体、癌及びその他の容態の診断及び処理 |
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US (10) | US7326415B2 (ja) |
EP (2) | EP1961767B1 (ja) |
JP (2) | JP4384852B2 (ja) |
CN (2) | CN101555283B (ja) |
AT (2) | ATE418565T1 (ja) |
AU (1) | AU2003235005B2 (ja) |
CA (1) | CA2434490C (ja) |
DE (1) | DE60230482D1 (ja) |
DK (2) | DK1360203T3 (ja) |
ES (2) | ES2383712T3 (ja) |
HK (3) | HK1070903A1 (ja) |
MY (1) | MY158262A (ja) |
PT (1) | PT1360203E (ja) |
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