JP2011525375A - 非溶血性llo融合タンパク質およびそれを利用する方法 - Google Patents
非溶血性llo融合タンパク質およびそれを利用する方法 Download PDFInfo
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Abstract
【選択図】図9
Description
別の実施形態では、本発明は、ヌクレオチド分子を含む免疫原性組成物を提供する。
各々の可能性は、本発明の個々の実施形態を表わす。
材料および実験的方法
下線を引いた配列は、配列の先頭から始まり、NdeI部位、NheI微、CBGコード領域、6×Hisタグ、およびBamHI部位である。次のステップで変異させるCBD残基をイタリック体の太字とした。
材料と実験的方法
ワクチン調製
Claims (30)
- リステオロジンO(LLO)タンパク質またはN末端断片を含む組換えタンパク質であって、
前記リステオロジンO(LLO)タンパク質またはN末端断片がコレステロール結合ドメイン(CBD)に突然変異を有し、前記突然変異が、
a.1〜50アミノ酸非LLOペプチドから配列番号18に記載される前記CBDの1〜50アミノ酸ペプチドへの置換、
b.配列番号37の残基C484、W491、もしくはW492またはこれらの組み合わせの突然変異、
あるいは
c.配列番号18に記載される前記CBDの1〜50アミノ酸ペプチドの欠失を含み、
前記組換えタンパク質の溶血作用が野生型のLLOと比較して100倍を上回る減少を示す、組換えタンパク質。 - 請求項1の組換えタンパク質であって、
前記LLOタンパク質またはN末端LLO断片がそのシグナルペプチド配列の欠失を含む、組換えタンパク質。 - 請求項1の組換えタンパク質であって、
前記LLOタンパク質またはN末端LLO断片がそのシグナルペプチド配列を含む、組換えタンパク質。 - 請求項1の組換えタンパク質であって、
前記LLOタンパク質の配列が配列番号37に記載されている、組換えタンパク質。 - 請求項1の組換えタンパク質であって、
前記組換えタンパク質が目的の異種ペプチドを含む、組換えタンパク質。 - 請求項5の組換えタンパク質であって、
前記非LLOペプチドが前記目的の異種ペプチドを含む、組換えタンパク質。 - 請求項5の組換えタンパク質であって、
前記目的の異種ペプチドが抗原ペプチドである、組換えタンパク質。 - 請求項7の組換えタンパク質であって、
前記抗原ペプチドが前立腺特異性抗原(PSA)ペプチドである、組換えタンパク質。 - 請求項7の組換えタンパク質であって、
前記抗原ペプチドがヒト乳頭腫ウイルス(HPV)E7ペプチドである、組換えタンパク質。 - 請求項7の組換えタンパク質であって、
前記抗原ペプチドがHer/2−neuペプチドである、組換えタンパク質。 - 請求項7の組換えタンパク質であって、
前記抗原ペプチドが、ヒト乳頭腫ウイルス(HPV)−16−E6、HPV−16−E7、HPV−18−E6、HPV−18−E7、前立腺特異性抗原(PSA)、前立腺幹細胞抗原(PSCA)、角質層キモトリプシン様酵素(SCCE)抗原、ウィルムス腫瘍抗原1(WT−1)、テロメラーゼ逆転写酵素(hTERT)、プロテイナーゼ3、チロシナーゼ関連タンパク質2(TRP2)、高分子量メラノーマ関連抗原(HMW−MAA)、滑膜肉腫、X(SSX)−2、癌胎児性抗原(CEA)、MAGE−A、インターロイキン−13受容体アルファ(IL13−Rアルファ)、炭酸脱水酵素IX(CAIX)、スルビビン、GP100、テスチシン、NY−ESO−1、またはB細胞受容体(BCR)である、組換えタンパク質。 - 請求項1の組換えタンパク質とアジュバントとを含むワクチン。
- 請求項12のワクチンであって、
前記アジュバントが、顆粒球・マクロファージコロニー刺激因子(GM−CSF)タンパク質、GM−GSFタンパク質をコードするヌクレオチド分子、サポニンQS21、モノホスホリル脂質A、または非メチル化CpG含有オリゴヌクレオチドを含む、ワクチン。 - 請求項1の組換えタンパク質と目的の異種ペプチドとを含む組成物であって、
前記組換えタンパク質が前記目的の異種ペプチドに共有結合していない、組成物。 - 請求項14の組成物とアジュバントとを含むワクチン。
- 請求項15のワクチンであって、
前記アジュバントが、顆粒球マクロファージコロニー刺激因子(GM−CSF)タンパク質、GM−GSFタンパク質をコードするヌクレオチド分子、サポニンQS21、モノホスホリル脂質A、または非メチル化CpG含有オリゴヌクレオチドを含む、ワクチン。 - 請求項1の組換えタンパク質をコードする組換えワクチンベクター。
- 請求項1の組換えタンパク質をコードするヌクレオチド分子。
- 請求項18のヌクレオチド分子とアジュバントを含むワクチン。
- 請求項1の組換えタンパク質を含む組換えリステリア菌株。
- 被験体の免疫応答を誘導する方法であって、
前記被験体に請求項7の組換えタンパク質を投与することで、前記抗原ペプチドに対する免疫応答を誘導すること、を含む方法。 - 被験体の免疫応答を誘導する方法であって、
前記被験体に請求項14の組成物を投与することで、前記目的の異種ペプチドに対する免疫応答を誘導すること、を含む方法。 - 被験体の免疫応答を誘導する方法であって、
前記被験体に請求項17の組換えワクチンベクターを投与することを含み、
前記組換えタンパク質の前記非LLOペプチドが目的の抗原ペプチドを含むことで、目的の前記抗原ペプチドに対する免疫応答を誘導する、方法。 - 被験体の免疫応答を誘導する方法であって、
前記被験体に請求項20の組換えリステリア菌株を投与することを含み、
前記組換えタンパク質の前記非LLOペプチドが目的の抗原ペプチドを含むことで、目的の前記抗原ペプチドに対する免疫応答を誘導する、方法。 - 卵巣メラノーマ細胞および肺癌細胞から選択されるNY−ESO−1発現癌細胞に対する被験体の免疫応答を誘導する方法であって、
前記被験体に請求項8の組換えタンパク質を投与することで、NY−ESO−1発現癌細胞に対する免疫応答を誘導するステップを含む、方法。 - 被験体の卵巣黒色腫および肺癌腫から選択されるNY−ESO−1発現腫瘍を処置、阻害、または抑制する方法であって、
前記被験体に請求項8の組換えタンパク質を投与することで、NY−ESO−1発現腫瘍を処置、阻害、または抑制するステップを含む、方法。 - 子宮頸癌細胞および頭頸部癌細胞から選択されるHPVE7発現癌細胞に対する被験体の免疫応答を誘導する方法であって、
前記被験体に請求項9の組換えタンパク質を投与することで、子宮頸癌細胞および頭頸部癌細胞から選択されるHPVE7発現癌細胞に対する免疫応答を誘導するステップを含む、方法。 - 被験体の子宮頸癌腫および頭頸部癌腫物から選択されるHPVE7発現腫瘍を処置、阻害、または抑制する方法であって、
前記被験体に請求項9の組換えタンパク質を投与することで、前記被験体の子宮頸癌腫および頭頸部癌腫物から選択されるHPVE7発現腫瘍を処置、阻害、または抑制するステップを含む、方法。 - B細胞受容体(BCR)発現リンパ腫に対する被験体の免疫応答を誘導する方法であって、
前記被験体に請求項10の組換えタンパク質を投与することで、BCR発現リンパ腫に対する免疫応答を誘導するステップを含む、方法。 - 被験体のB細胞受容体(BCR)発現リンパ腫を処置、阻害、または抑制する方法であって、
前記被験体に請求項10の組換えタンパク質を投与することで、被験体のB細胞受容体(BCR)発現リンパ腫を処置、阻害、または抑制するステップを含む、方法。
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DK2942355T3 (en) | 2019-04-08 |
PL2942355T3 (pl) | 2020-04-30 |
US8771702B2 (en) | 2014-07-08 |
HUE042819T2 (hu) | 2019-07-29 |
US10189885B2 (en) | 2019-01-29 |
US9499602B2 (en) | 2016-11-22 |
JP6114237B2 (ja) | 2017-04-12 |
EP2307049B1 (en) | 2016-11-02 |
EP2307049A1 (en) | 2011-04-13 |
EP2942355B1 (en) | 2018-12-19 |
DK2307049T3 (en) | 2017-01-23 |
EP2942355A1 (en) | 2015-11-11 |
US20140248304A1 (en) | 2014-09-04 |
US20160024173A1 (en) | 2016-01-28 |
HK1217341A1 (zh) | 2017-01-06 |
ES2719832T3 (es) | 2019-07-16 |
EP2307049A4 (en) | 2012-12-26 |
ES2609925T3 (es) | 2017-04-25 |
WO2010008782A1 (en) | 2010-01-21 |
PT2307049T (pt) | 2017-02-10 |
PT2942355T (pt) | 2019-05-13 |
JP5597197B2 (ja) | 2014-10-01 |
JP2015017096A (ja) | 2015-01-29 |
PL2942355T4 (pl) | 2020-04-30 |
EP3530669A1 (en) | 2019-08-28 |
US20090081248A1 (en) | 2009-03-26 |
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