JP2018135355A - リステリアの抗原配列の発現を容易にするシグナルペプチド融合パートナー、ならびにその調製方法およびその使用 - Google Patents
リステリアの抗原配列の発現を容易にするシグナルペプチド融合パートナー、ならびにその調製方法およびその使用 Download PDFInfo
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- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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Abstract
【解決手段】非リステリア抗原に対する免疫応答を刺激するための、リステリア細菌を含む組成物。リステリア細菌の有効量をヒトに投与することを含み、リステリア細菌は非リステリア抗原を融合タンパク質として発現し、融合タンパク質は、分泌リステリアタンパク質配列の組み換え修飾によって生じるポリペプチドと非リステリア抗原を含み、分泌リステリアタンパク質配列が、その非修飾形においてシグナル配列および1以上のPESTモチーフを含み、修飾が、ポリペプチドがいずれのPESTモチーフを欠如するような、1以上の残基による欠失もしくは置換による各PESTモチーフの除去を含み、分泌リステリアタンパク質配列はActAまたはLLOであり、非リステリア抗原は前記ヒトの1以上の細胞内で発現する組成物。
【選択図】図1
Description
(a)プロモーターと、
(b)前述のプロモーターに作動可能に結合した核酸とを含むポリヌクレオチドに関し、
前述の核酸は分泌リステリアタンパク質配列の組換え修飾に由来するポリペプチドを含む融合タンパク質と、非リステリア抗原とをコードし、前述の分泌リステリアタンパク質配列はその非修飾形においてシグナル配列および1以上のPESTモチーフを含み、前述の修飾はポリペプチドがいずれのPESTモチーフを欠如するような欠失による、または1以上の残基による置換による各PESTモチーフの除去を含む。
1.定義
(1)疎水性:ノルロイシン、Ile、Val、Leu、Phe、Cys、Met
(2)中性の親水性:Cys、Ser、Thr
(3)酸性:Asp、Glu
(4)塩基性:Asn、Gln、His、Lys、Arg
(5)鎖配向に影響する残基:Gly、Pro
(6)芳香族:Trp、Tyr,Phe、および
(7)小アミノ酸:Gly、Ala、Ser
のうちの基の一つにあるアミノ酸と、異なる基の別のアミノ酸との交換である。
Arg:−4.5 Ser:−0.8 Lys:−3.9
Thr:−0.7 Asn:−3.5 Gly:−0.4
Asp:−3.5 Ala:1.8 Gln:−3.5
Met:1.9 Glu:−3.5 Cys:2.5
His:−3.2 Phe:2.8 Pro:−1.6
Leu:3.8 Tyr:−1.3 Val:4.2
Trp:−0.9 Ile:4.5
ハイドロパシー指数=10*Kyte−Doolittleハイドロパシー指数+45
PESTスコア=0.55*DEPST−0.5*疎水性指数。
抗原コンストラクト
標的抗原
VGLNRFMRAM MVVFITANCI TINPDIIFAA TDSEDSSLNT DEWEEEKTEE 50
QPSEVNTGPR YETAREVSSR DIEELEKSNK VKNTNKADLI AMLKAKAEKG 100
MGLNRFMRAM MVVFITANCI TINPDIIFAA TDSEDSSLNT DEWEEEKTEE 50
QPSEVNTGPR YETAREVSSR DIEELEKSNK VKNTNKADLI AMLKAKAEKG 100
VGLNRFMRAM MVVFITANCI TINPDIIFAA TDSEDSSLNT DEWEEEKTEE 50
QPSEVNTGPR YETAREVSSR DIEELEKSNK VKNTNKADLI AMLKAKAEKG 100
GS
第1の残基メチオニンで合成される場合、以下の配列を有する。
MGLNRFMRAM MVVFITANCI TINPDIIFAA TDSEDSSLNT DEWEEEKTEE 50
QPSEVNTGPR YETAREVSSR DIEELEKSNK VKNTNKADLI AMLKAKAEKG 100
GS。
このように、本発明の修飾ActAは、以下の配列(ダッシュは欠失を示し、太字のテキストは置換を示す)を含むか、またはこれからなってもよい。
10 20 30 40 50 60
MKKIMLVFIT LILVSLPIAQ QTEAKDASAF NKENSISSMA PPASPPASPK TPIEKKHADE
70 80 90 100 110 120
IDKYIQGLDY NKNNVLVYHG DAVTNVPPRK GYKDGNEYIV VEKKKKSINQ NNADIQVVNA
130 140 150 160 170 180
ISSLTYPGAL VKANSELVEN QPDVLPVKRD SLTLSIDLPG MTNQDNKIVV KNATKSNVNN
190 200 210 220 230 240
AVNTLVERWN EKYAQAYPNV SAKIDYDDEM AYSESQLIAK FGTAFKAVNN SLNVNFGAIS
250 260 270 280 290 300
EGKMQEEVIS FKQIYYNVNV NEPTRPSRFF GKAVTKEQLQ ALGVNAENPP AYISSVAYGR
310 320 330 340 350 360
QVYLKLSTNS HSTKVKAAFD AAVSGKSVSG DVELTNIIKN SSFKAVIYGG SAKDEVQIID
370 380 390 400 410 420
GNLGDLRDIL KKGATFNRET PGVPIAYTTN FLKDNELAVI KNNSEYIETT SKAYTDGKIN
430 440
IDHSGGYVAQ FNISWDEVNY D
KE−−−−−−− −−−−−−−−−−またはその完全な欠失。これは、例示のみを目的とする。
実施例
実施例1.
実施例2.
実施例3.
実施例4.
実施例5.
実施例6.
実施例7.
Claims (17)
- ヒトにおいて、非リステリア抗原に対する免疫応答を刺激するための方法に使用するための、リステリア細菌を含む組成物であって、
前記方法は、前記リステリア細菌の有効量を前記ヒトに投与することを含み、前記リステリア細菌は前記非リステリア抗原を融合タンパク質として発現し、
前記融合タンパク質は、分泌リステリアタンパク質配列の組み換え修飾によって生じるポリペプチドと非リステリア抗原を含み、前記分泌リステリアタンパク質配列が、その非修飾形においてシグナル配列および1以上のPESTモチーフを含み、前記修飾が、前記ポリペプチドがいずれのPESTモチーフを欠如するような、1以上の残基による欠失もしくは置換による前記各PESTモチーフの除去を含み、前記分泌リステリアタンパク質配列はActAまたはLLOであり、
前記非リステリア抗原は前記ヒトの1以上の細胞内で発現する、組成物。 - 前記修飾が、前記分泌リステリアタンパク質配列の約100残基における切り詰めをさらに含む、請求項1に記載の組成物。
- 前記ポリペプチドが前記分泌リステリアタンパク質配列のシグナル配列を非修飾形で保持する、請求項1に記載の組成物。
- 前記修飾が、
前記分泌リステリアタンパク質配列の前記シグナル配列の一部ではない1以上の疎水性ドメインの除去、および/または
前記分泌リステリアタンパク質配列の前記シグナル配列の一部ではない1以上の疎水性ドメイン内の1以上の残基の、非疎水性アミノ酸との置換をさらに含む、
請求項1に記載の組成物。 - 前記分泌リステリアタンパク質配列がActA配列であり、配列KTEEQPSEVNTGPの少なくとも75%が除去されている、請求項1に記載の組成物。
- 配列KTEEQPSEVNTGPまたはKTEEQPSEVNTGPRが除去されている、請求項1に記載の組成物。
- 前記分泌リステリアタンパク質配列がActA配列であり、配列KTEEQPSEVNTGPR中の1以上のP、E、SおよびT残基がP、E、SおよびT以外の残基と置換されている、請求項1に記載の組成物。
- 前記配列KTEEQPSEVNTGPR中の各P、E、SおよびT残基がKまたはRと置換されている、請求項7に記載の組成物。
- 前記分泌リステリアタンパク質配列がActA配列であり、配列LIAML内の1以上の疎水性残基が非疎水性アミノ酸と置換されている、請求項1に記載の組成物。
- 前記配列LIAMLが配列QDNKRに置き換えられている、請求項9に記載の組成物。
- 前記ポリペプチドが図2のdlPESTおよびdlPEST qdnkrと呼ばれる配列の一つの少なくとも最初の95残基を含む、請求項1に記載の組成物。
- 前記分泌リステリアタンパク質配列がLLO配列であり、配列SISSMAPPASPPASPKTPIEの少なくとも75%が除去されている、請求項1に記載の組成物。
- 配列KENSISSMAPPASPPASPKまたはNSISSMAPPASPPASPKTPIEKKHADが除去されている、請求項1に記載の組成物。
- 前記分泌リステリアタンパク質配列がLLO配列であり、配列SISSMAPPASPPASPKTPIEKKHAD中の1以上のP、E、SおよびT残基がP、E、SおよびT以外の残基と置換されている、請求項1に記載の組成物。
- 前記配列SISSMAPPASPPASPKTPIEKKHAD中の各P、E、SおよびT残基がKまたはRと置換されている、請求項14に記載の組成物。
- 前記ポリペプチドが図2のLLO dlPESTおよびLLO dl26と呼ばれる配列の一つの少なくとも最初の95残基を含む、請求項1に記載の組成物。
- 前記非リステリア抗原ががん細胞、腫瘍または感染病原体抗原である、請求項1に記載の組成物。
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-
2013
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CN110499324A (zh) * | 2019-09-02 | 2019-11-26 | 中生康元生物科技(北京)有限公司 | 一种用于鉴定肿瘤新抗原的细菌表达载体及筛选鉴定肿瘤新抗原的方法 |
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JP6671408B2 (ja) | 2020-03-25 |
CN104955835B (zh) | 2020-04-17 |
CN104955835A (zh) | 2015-09-30 |
AU2013370210A8 (en) | 2016-06-23 |
EP2938627A4 (en) | 2016-12-14 |
EA201590397A1 (ru) | 2016-02-29 |
HK1215260A1 (zh) | 2016-08-19 |
EP2938627A1 (en) | 2015-11-04 |
CA2888727A1 (en) | 2014-07-03 |
WO2014106123A8 (en) | 2016-06-16 |
BR112015015076A2 (pt) | 2018-10-30 |
SG11201502792TA (en) | 2015-05-28 |
KR20150099738A (ko) | 2015-09-01 |
JP2016503655A (ja) | 2016-02-08 |
AU2013370210A1 (en) | 2015-06-18 |
EA201590397A8 (ru) | 2016-08-31 |
EP2938627B1 (en) | 2019-03-20 |
US9663557B2 (en) | 2017-05-30 |
SG10201700916SA (en) | 2017-03-30 |
US20170253637A1 (en) | 2017-09-07 |
AU2018203555A1 (en) | 2018-06-07 |
WO2014106123A1 (en) | 2014-07-03 |
US20140186387A1 (en) | 2014-07-03 |
KR102160322B1 (ko) | 2020-09-25 |
AU2013370210B2 (en) | 2018-06-14 |
MX2015008329A (es) | 2016-03-01 |
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