JP5757863B2 - 異種抗原のための二重送達システム - Google Patents
異種抗原のための二重送達システム Download PDFInfo
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Description
ctggaagaacaaaggtctctgggtccccgagggccagcgggccaggatcaccgtggctgctctggatgcctccaatctcttggccagcgttccatcaccccagcgctcagagcatgatgtgctcttccaggtcacacagttccccagccggggccagctgttggtgtccgaggagcccctccatgctgggcagccccacttcctgcagtcccagctggctgcagggcagctagtgtatgcccacggcggtgggggcacccagcaggatggcttccactttcgtgcccacctccaggggccagcaggggcctccgtggctggaccccaaacctcagaggcctttgccatcacggtgagggatgtaaatgagcggccccctcagccacaggcctctgtcccactccggctcacccgaggctctcgtgcccccatctcccgggcccagctgagtgtggtggacccagactcagctcctggggagattgagtacgaggtccagcgggcaccccacaacggcttcctcagcctggtgggtggtggcctggggcccgtgacccgcttcacgcaagccgatgtggattcagggcggctggccttcgtggccaacgggagcagcgtggcaggcatcttccagctgagcatgtctgatggggccagcccacccctgcccatgtccctggctgtggacatcctaccatccgccatcgaggtgcagctgcgggcacccctggaggtgccccaagctttggggcgctcctcactgagccagcagcagctccgggtggtttcagatcgggaggagccagaggcagcataccgcctcatccagggaccccagtatgggcatctcctggtgggcgggcggcccacctcggccttcagccaattccagatagaccagggcgaggtggtctttgccttcaccaacttctcctcctctcatgaccacttcagagtcctggcactggctaggggtgtcaatgcatcagccgtagtgaacgtcactgtgagggctctgctgcatgtgtgggcaggtgggccatggccccagggtgccaccctgcgcctggaccccaccgtcctagatgctggcgagctggccaaccgcacaggcagtgtgccgcgcttccgcctcctggagggaccccggcatggccgcgtggtccgcgtgccccgagccaggacggagcccgggggcagccagctggtggagcagttcactcagcaggaccttgaggacgggaggctggggctggaggtgggcaggccagaggggagggcccccggccccgcaggtgacagtctcactctggagctgtgggcacagggcgtcccgcctgctgtggcctccctggactttgccactgagccttacaatgctgcccggccctacagcgtggccctgctcagtgtccccgaggccgcccggacggaagcagggaagccagagagcagcacccccacaggcgagccaggccccatggcatccagccctgagcccgctgtggccaagggaggcttcctgagcttccttgaggccaacatgttcagcgtcatcatccccatgtgcctggtacttctgctcctggcgctcatcctgcccctgctcttctacctccgaaaacgcaacaagacgggcaagcatgacgtccaggtcctgactgccaagccccgcaacggcctggctggtgacaccgagacctttcgcaaggtggagccaggccaggccatcccgctcacagctgtgcctggccaggggccccctccaggaggccagcctgacccagagctgctgcagttctgccggacacccaaccctgcccttaagaatggccagtactgggtgtgaggcctggcctgggcccagatgctgatcgggccagggacaggc(配列番号20)。別の実施形態では、組み換えヌクレオチドは、配列番号20に記載される配列を有する。別の実施形態では、本明細書において提供される方法および組成物のHMW−MAAをコードするヌクレオチドは、配列番号20に記載される配列を含む。別の実施形態では、HMW−MAAをコードするヌクレオチドは、配列番号20の相同体である。別の実施形態では、HMW−MAAをコードするヌクレオチドは、配列番号20の変異形である。別の実施形態では、HMW−MAAをコードするヌクレオチドは、配列番号20の断片である。別の実施形態では、HMW−MAAをコードするヌクレオチドは、配列番号20のイソ型である。各可能性は、本明細書において提供される方法および組成物の個別の実施形態を表す。
tggaaggtggcctctgtgaggagccacggggacagcatcctgcagatggtcctggcccttgtcccaccgacctgtctacaaggactgtcctcgtggaccctcccctctgcacaggagctggaccctgaagtcccttcctaccggccaggactggagcccctacccctctgttggaatccctgcccaccttcttctggaagtcggctctggagacatttctctcttcttccaaagctgggaactgctatctgttatctgcctgtccaggtctgaaagataggattgcccaggcagaaactgggactgacctatctcactctctccctgcttttacccttagggtgattctgggggcccacttgtctgtaatggtgtgcttcaaggtatcacgtcatggggcagtgaaccatgtgccctgcccgaaaggccttccctgtacaccaaggtggtgcattaccggaagtggatcaaggacaccatcgtggccaacccctgagcacccctatcaagtccctattgtagtaaacttggaaccttggaaatgaccaggccaagactcaagcctccccagttctactgacctttgtccttaggtgtgaggtccagggttgctaggaaaagaaatcagcagacacaggtgtagaccagagtgtttcttaaatggtgtaattttgtcctctctgtgtcctggggaatactggccatgcctggagacatatcactcaatttctctgaggacacagttaggatggggtgtctgtgttatttgtgggatacagagatgaaagaggggtgggatcc(配列番号22;GenBank受入番号X14810)。別の実施形態では、KLK3タンパク質は、配列番号24の残基401..446、1688..1847、3477..3763、3907..4043、および5413..5568によってコードされる。別の実施形態では、KLK3タンパク質は、配列番号24の相同体によってコードされる。別の実施形態では、KLK3タンパク質は、配列番号24の変異体によってコードされる。別の実施形態では、KLK3タンパク質は、配列番号24の異性体によってコードされる。別の実施形態では、KLK3タンパク質は、配列番号24の断片によってコードされる。各可能性は、本明細書において提供される方法および組成物の個別の実施形態を表す。
gaaaataaaacccgcactatgccattacatttatatctatgatacgtgtttgtttttctttgctggctagcttaattgcttatatttacctgcaataaaggatttcttacttccattatactcccattttccaaaaacatacggggaacacgggaacttattgtacaggccacctcatagttaatggtttcgagccttcctgcaatctcatccatggaaatatattcatccccctgccggcctattaatgtgacttttgtgcccggcggatattcctgatccagctccaccataaattggtccatgcaaattcggccggcaattttcaggcgttttcccttcacaaggatgtcggtccctttcaattttcggagccagccgtccgcatagcctacaggcaccgtcccgatccatgtgtctttttccgctgtgtactcggctccgtagctgacgctctcgccttttctgatcagtttgacatgtgacagtgtcgaatgcagggtaaatgccggacgcagctgaaacggtatctcgtccgacatgtcagcagacgggcgaaggccatacatgccgatgccgaatctgactgcattaaaaaagccttttttcagccggagtccagcggcgctgttcgcgcagtggaccattagattctttaacggcagcggagcaatcagctctttaaagcgctcaaactgcattaagaaatagcctctttctttttcatccgctgtcgcaaaatgggtaaatacccctttgcactttaaacgagggttgcggtcaagaattgccatcacgttctgaacttcttcctctgtttttacaccaagtctgttcatccccgtatcgaccttcagatgaaaatgaagagaaccttttttcgtgtggcgggctgcctcctgaagccattcaacagaataacctgttaaggtcacgtcatactcagcagcgattgccacatactccgggggaaccgcgccaagcaccaatataggcgccttcaatccctttttgcgcagtgaaatcgcttcatccaaaatggccacggccaagcatgaagcacctgcgtcaagagcagcctttgctgtttctgcatcaccatgcccgtaggcgtttgctttcacaactgccatcaagtggacatgttcaccgatatgttttttcatattgctgacattttcctttatcgcggacaagtcaatttccgcccacgtatctctgtaaaaaggttttgtgctcatggaaaactcctctcttttttcagaaaatcccagtacgtaattaagtatttgagaattaattttatattgattaatactaagtttacccagttttcacctaaaaaacaaatgatgagataatagctccaaaggctaaagaggactataccaactatttgttaattaa(配列番号46)。このプラスミドは、2−20−08に大腸菌からGenewiz施設で配列された。
Claims (26)
- 第1の核酸分子と第2の核酸分子とを含む組み換えリステリア株であって、それぞれの前記核酸分子は、異種抗原ポリペプチドまたはその免疫原性断片をコードし、前記第1の核酸分子は、内因性PEST含有遺伝子を伴うオープンリーディングフレームにおいてリステリアゲノムに組み込まれ、前記組み換えリステリア株は、異種抗原をコードする前記第2の核酸分子を含むエピソーム発現ベクターを含み、前記組み換えリステリア株が、内因性dal、dat、及びActA遺伝子における欠失変異を含み、前記欠失変異の結果、弱毒化された栄養要求性リステリア株となっていることを特徴とする組み換えリステリア株。
- 異種抗原をコードする前記第2の核酸分子は、PEST含有ポリペプチドをコードする核酸配列を伴うオープンリーディングフレームにおける前記エピソーム発現ベクターに存在する、請求項1に記載の組み換えリステリア株。
- 前記PEST含有遺伝子は、LLOまたはActAである、請求項1に記載の組み換えリステリア株。
- 前記第1の核酸分子または前記第2の核酸分子は、腫瘍細胞によって発現される血管新生ポリペプチドをコードする、請求項1に記載の組み換えリステリア株。
- 前記第1の核酸分子または前記第2の核酸分子は、前立腺特異抗原(PSA)または高分子量メラノーマ関連抗原(HMW−MAA)をコードする、請求項1に記載の組み換えリステリア株。
- 前記第1の核酸分子は、リステリアゲノムへの部位特異的相同的組み換えのために設計されるベクターである、請求項1に記載の組み換えリステリア株。
- 前記組み換えリステリア株は、動物宿主に継代された、請求項1に記載の組み換えリステリア株。
- 前記組み換えリステリア株は、組み換えリステリアモノサイトゲネス株である、請求項1に記載の組み換えリステリア株。
- 対象者における抗原に対する免疫応答を誘導するための薬剤を製造するための組み換えリステリア株の使用であって、前記組み換えリステリア株は、第1の核酸分子と第2の核酸分子とを含み、それぞれの前記核酸分子は、異種抗原ポリペプチドまたはその免疫原性断片をコードし、前記第1の核酸分子は、内因性PEST含有遺伝子を伴うオープンリーディングフレームにおいてリステリアゲノムに機能可能に組み込まれ、前記組み換えリステリア株は、異種抗原をコードする前記第2の核酸分子を含むエピソーム発現ベクターを含み、前記組み換えリステリア株が、内因性dal、dat、及びActA遺伝子における欠失変異を含み、前記欠失変異の結果、弱毒化された栄養要求性リステリア株となっていることを特徴とする使用。
- 異種抗原をコードする前記第2の核酸分子は、PEST含有ポリペプチドをコードする核酸配列を伴うオープンリーディングフレームにおける前記エピソーム発現ベクターに存在する、請求項9に記載の使用。
- 前記PEST含有遺伝子は、LLOまたはActAである、請求項9若しくは10に記載の使用。
- 前記第1の核酸分子または前記第2の核酸分子は、腫瘍細胞によって発現される血管新生ポリペプチドをコードする、請求項9乃至11のいずれか一項に記載の使用。
- 前記第1の核酸分子または前記第2の核酸分子は、前立腺特異抗原(PSA)または高分子量メラノーマ関連抗原(HMW−MAA)をコードする、請求項9乃至12のいずれか一項に記載の使用。
- 前記第1の核酸分子は、リステリアゲノムへの部位特異的相同的組み換えのために設計されるベクターである、請求項9乃至13のいずれか一項に記載の使用。
- 前記第1の核酸分子は、部位特異的インテグラーゼ遺伝子を含む、請求項9乃至13のいずれか一項に記載の使用。
- 前記部位特異的インテグラーゼ遺伝子は、A118またはU153である、請求項15に記載の使用。
- 前記ベクターは、ファージ組み込みベクターである、請求項14に記載の使用。
- 前記組み換えリステリア株は、動物宿主に継代された、請求項9乃至15のいずれか一項に記載の使用。
- 前記組み換えリステリア株は、組み換えリステリアモノサイトゲネス株である、請求項9乃至15、及び18のいずれか一項に記載の使用。
- 前記薬剤は、経口または非経口で投与される薬剤である、請求項9乃至15、18、及び19のいずれか一項に記載の使用。
- 対象者における癌を治療、抑制、または阻害するための薬剤を製造するための、請求項1乃至8のいずれか一項に記載の組み換えリステリア株の使用。
- 前記癌は、前立腺癌、卵巣癌、乳癌、脳癌、肺癌、消化管癌、メラノーマ、膵臓癌、肉腫、またはそれらの組み合わせである、請求項21に記載の使用。
- 2つの抗原を発現する組み換えリステリア株を製造する方法であって、
(a)第1の抗原をコードする第1の核酸を、内因性PEST含有遺伝子を伴うオープンリーディングフレームにおいてリステリアゲノムに遺伝子的に融合すること、
(b)第2の抗原をコードする第2の核酸を含むエピソーム発現ベクターで、前記組み換えリステリアを形質転換すること、および
(c)前記組み換えリステリア株における抗原発現を促す条件下で前記第1の抗原および前記第2の抗原を発現すること、
を含み、
前記組み換えリステリア株が、内因性dal、dat、及びActA遺伝子における欠失変異を含み、前記欠失変異の結果、弱毒化された栄養要求性リステリア株となっていることを特徴とすることを特徴とする方法。 - 前記第1の核酸分子は、部位特異的インテグラーゼ遺伝子を含む、請求項23に記載の方法。
- 前記部位特異的インテグラーゼ遺伝子は、A118またはU153である、請求項24に記載の方法。
- 前記ベクターは、ファージ組み込みベクターである、請求項23に記載の方法。
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WO2009143167A3 (en) | 2010-01-14 |
WO2009143167A2 (en) | 2009-11-26 |
US9644212B2 (en) | 2017-05-09 |
US20140314708A1 (en) | 2014-10-23 |
JP2015213500A (ja) | 2015-12-03 |
JP2017195888A (ja) | 2017-11-02 |
US20110129499A1 (en) | 2011-06-02 |
JP6182172B2 (ja) | 2017-08-16 |
EP2853269A1 (en) | 2015-04-01 |
EP2288379A4 (en) | 2012-08-08 |
EP2288379A2 (en) | 2011-03-02 |
ES2741730T3 (es) | 2020-02-12 |
HK1207315A1 (en) | 2016-01-29 |
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EP2853269B1 (en) | 2019-05-01 |
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