JP2015213500A - 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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Abstract
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 (82)
- 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る、組み換えリステリア株。
- 前記組み換えリステリア株は、ファゴリソソームから抜け出ることが可能である、請求項1に記載の組み換えリステリア株。
- 前記第2の核酸分子は、前記内因性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、前記第1の核酸分子と共にリステリアゲノムに機能可能に組み込まれる、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、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む、請求項1に記載の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4に記載の組み換えリステリア株。
- 前記PEST含有遺伝子は、LLOである、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、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、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)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、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。
- 前記断片は、免疫原性断片である、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、栄養要求性リステリア株である、請求項1に記載の組み換えリステリア株。
- 前記栄養要求性リステリア株は、dal/dat変異体である、請求項14に記載の組み換えリステリア株。
- 前記栄養要求性リステリア株は、前記栄養要求性リステリア株の栄養要求性を補完する代謝酵素を含むエピソーム発現ベクターを含む、請求項14に記載の組み換えリステリア株。
- 前記代謝酵素は、アミノ酸代謝酵素である、請求項16に記載の組み換えリステリア株。
- 前記代謝酵素は、前記組み換えリステリア株における細胞壁合成のために使用されるアミノ酸の形成を触媒する、請求項16に記載の組み換えリステリア株。
- 前記代謝酵素は、アラニンラセマーゼ酵素である、請求項16に記載の組み換えリステリア株。
- 前記代謝酵素は、D−アミノ酸トランスフェラーゼ酵素である、請求項16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ている、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、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。
- 請求項1に記載の組み換えリステリア株と、アジュバント、サイトカイン、ケモカイン、またはそれらの組み合わせとを含む、ワクチン。
- 組み換えリステリア株を対象に投与することを含む、前記対象における抗原に対する免疫応答を誘導する方法であって、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る、方法。
- 前記組み換えリステリア株は、ファゴリソソームから抜け出ることが可能である、請求項24に記載の方法。
- 前記第2の核酸分子は、前記内因性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、前記第1の核酸分子と共にリステリアゲノムに機能可能に組み込まれる、請求項24に記載の方法。
- 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む、請求項24に記載の方法。
- 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27に記載の方法。
- 前記PEST含有遺伝子は、LLOである、請求項24に記載の方法。
- 前記PEST含有遺伝子は、ActAである、請求項24に記載の方法。
- 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ポリペプチドをコードする、請求項24に記載の方法。
- 前記第1の核酸分子または前記第2の核酸分子は、血管新生ポリペプチドをコードする、請求項24に記載の方法。
- 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)をコードする、請求項24に記載の方法。
- 前記第1の核酸分子または前記第2の核酸分子は、高分子量メラノーマ関連抗原(HMW−MAA)をコードする、請求項24に記載の方法。
- 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24に記載の方法。
- 前記断片は、免疫原性断片である、請求項24に記載の方法。
- 前記組み換えリステリア株は、栄養要求性リステリア株である、請求項24に記載の方法。
- 前記栄養要求性リステリア株は、dal/dat変異体である、請求項37に記載の方法。
- 前記栄養要求性リステリア株は、前記栄養要求性リステリア株の栄養要求性を補完する代謝酵素を含むエピソーム発現ベクターを含む、請求項37に記載の方法。
- 前記代謝酵素は、アミノ酸代謝酵素である、請求項39に記載の方法。
- 前記代謝酵素は、前記組み換えリステリア株における細胞壁合成のために使用されるアミノ酸の形成を触媒する、請求項40に記載の方法。
- 前記代謝酵素は、アラニンラセマーゼ酵素である、請求項40に記載の方法。
- 前記代謝酵素は、D−アミノ酸トランスフェラーゼ酵素である、請求項40に記載の方法。
- 前記組み換えリステリア株は、動物宿主に継代されている、請求項24に記載の方法。
- 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24に記載の方法。
- 前記組み換えリステリア株は、アジュバント、サイトカイン、ケモカイン、またはそれらの組み合わせと共に投与される、請求項24に記載の方法。
- 前記組み換えリステリア株は、経口または非経口で投与される、請求項24に記載の方法。
- 請求項1に記載の組み換えリステリア株を対象に投与することを含む、前記対象における癌を治療、抑制、または阻害する方法。
- 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)をコードする、請求項48に記載の方法。
- 前記癌は、前立腺癌である、請求項49に記載の方法。
- 前記癌は、卵巣癌、乳癌、またはそれらの組み合わせである、請求項49に記載の方法。
- 前記第1の核酸分子または前記第2の核酸分子は、高分子量メラノーマ関連抗原(HMW−MAA)をコードする、請求項48に記載の方法。
- 前記癌は、メラノーマである、請求項52に記載の方法。
- 前記癌は、乳癌、脳癌、肺癌、消化管癌、肉腫、膵臓癌、またはそれらの組み合わせである、請求項52に記載の方法。
- 請求項1に記載の組み換えリステリア株を対象に投与することを含む、前記対象における少なくとも1つの腫瘍を治療、抑制、または阻害する方法。
- 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)をコードする、請求項55に記載の方法。
- 前記腫瘍は、前立腺腫瘍である、請求項56に記載の方法。
- 前記腫瘍は、卵巣腫瘍、乳房腫瘍、またはそれらの組み合わせである、請求項56に記載の方法。
- 前記第1の核酸分子または前記第2の核酸分子は、高分子量メラノーマ関連抗原(HMW−MAA)をコードする、請求項55に記載の方法。
- 腫瘍は、乳房腫瘍である、請求項59に記載の方法。
- 前記腫瘍は、脳腫瘍、肺腫瘍、消化管腫瘍、膵臓腫瘍、またはそれらの組み合わせである、請求項59に記載の方法。
- 異種抗原ポリペプチドまたはその断片をコードする核酸分子を含む組み換えリステリア株であって、前記核酸分子は、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る、組み換えリステリア株。
- 前記組み換えリステリア株は、ファゴリソソームから抜け出ることが可能である、請求項62に記載の組み換えリステリア株。
- 前記PEST含有遺伝子は、LLOである、請求項62に記載の組み換えリステリア株。
- 前記PEST含有遺伝子は、ActAである、請求項62に記載の組み換えリステリア株。
- 前記核酸分子は、腫瘍細胞によって発現されるポリペプチドをコードする、請求項62に記載の組み換えリステリア株。
- 前記核酸分子は、血管新生ポリペプチドをコードする、請求項62に記載の組み換えリステリア株。
- 前記核酸分子は、前立腺特異抗原(PSA)をコードする、請求項62に記載の組み換えリステリア株。
- 前記核酸分子は、高分子量メラノーマ関連抗原(HMW−MAA)をコードする、請求項62に記載の組み換えリステリア株。
- 前記核酸分子は、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62に記載の組み換えリステリア株。
- 前記断片は、免疫原性断片である、請求項62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、栄養要求性リステリア株である、請求項62に記載の組み換えリステリア株。
- 前記栄養要求性リステリア株は、dal/dat変異体である、請求項62に記載の組み換えリステリア株。
- 前記栄養要求性リステリア株は、前記栄養要求性リステリア株の栄養要求性を補完する代謝酵素を含むエピソーム発現ベクターを含む、請求項72に記載の組み換えリステリア株。
- 前記代謝酵素は、アミノ酸代謝酵素である、請求項74に記載の組み換えリステリア株。
- 前記代謝酵素は、前記組み換えリステリア株における細胞壁合成のために使用されるアミノ酸の形成を触媒する、請求項74に記載の組み換えリステリア株。
- 前記代謝酵素は、アラニンラセマーゼ酵素である、請求項74に記載の組み換えリステリア株。
- 前記代謝酵素は、D−アミノ酸トランスフェラーゼ酵素である、請求項76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ている、請求項62に記載の組み換えリステリア。
- 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62に記載の組み換えリステリア。
- 2つの抗原を発現する組み換えリステリア株を産生する方法であって、
(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、
を含む、方法。 - 2つの抗原を発現する組み換えリステリア株を産生する方法であって、
(a)第1の抗原をコードする第1の核酸および第2の抗原をコードする第2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、および
(b)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の抗体および前記第2の抗原を発現すること、
を含む、方法。
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JP5757863B2 (ja) | 2015-08-05 |
US20140314708A1 (en) | 2014-10-23 |
WO2009143167A2 (en) | 2009-11-26 |
DK2853269T3 (da) | 2019-08-05 |
EP2853269B1 (en) | 2019-05-01 |
US20110129499A1 (en) | 2011-06-02 |
JP6182172B2 (ja) | 2017-08-16 |
EP2288379A4 (en) | 2012-08-08 |
HK1207315A1 (en) | 2016-01-29 |
JP2011529684A (ja) | 2011-12-15 |
JP2017195888A (ja) | 2017-11-02 |
WO2009143167A3 (en) | 2010-01-14 |
EP2853269A1 (en) | 2015-04-01 |
EP2288379A2 (en) | 2011-03-02 |
US9644212B2 (en) | 2017-05-09 |
ES2741730T3 (es) | 2020-02-12 |
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