JP5456464B2 - ポックスウイルスおよびポックスウイルス組成物の製造方法 - Google Patents
ポックスウイルスおよびポックスウイルス組成物の製造方法 Download PDFInfo
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- JP5456464B2 JP5456464B2 JP2009515747A JP2009515747A JP5456464B2 JP 5456464 B2 JP5456464 B2 JP 5456464B2 JP 2009515747 A JP2009515747 A JP 2009515747A JP 2009515747 A JP2009515747 A JP 2009515747A JP 5456464 B2 JP5456464 B2 JP 5456464B2
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Description
a) パッケージング細胞の培養物を調製し、
b) 前記細胞培養物を感染させ、
c) 前記感染細胞を適当な時間培養し、
d) 培養物上清および/またはパッケージング細胞から産生したポックスウイルス粒子を回収し、
e) 必要に応じて、回収したポックスウイルス粒子を精製する
工程を含んでなる、方法も提供する。
A. CEFの調製
66個のSPF卵を、2%ホルモール溶液中で60秒間インキュベーションする。70%エタノールで洗浄した後、卵を開いて胚を抽出し分析する。次に、得られた組織をジスパーゼ(Ul/ml)およびトリプル・セレクト(triple select)(Ul/ml)によって36.5℃で120分間消化する。
CEFをVP−SFM(invitrogen社)55l中で36.5℃にて2日間インキュベーションする。次に、細胞培地を廃棄し、ポックスウイルス(0.05 MOI)をイーグル基礎培地(invitrogen社)55 lに加える。次に、感染パッケージング細胞を、3日間インキュベーションする。
パッケージング細胞と細胞培地を集める。次に、混合物を、Silverson(商品名)L4R高速ホモジナイザーを用いて15分間ホモジナイズする。得られた混合物を、次にSartopure 5μm (Sartorius)に連結したSartopure 8μm上で1 l/分の流速の深層濾過によって透明にする。
A. HPV抗原を発現する腫瘍を有するマウスの治療投与
それぞれのベクター構造の名称および簡単な説明
TG4001: HPVタンパク質、E6およびE7(プロモーターp7.5の制御下)およびIL2(プロモーターpH5Rの制御下)のコード配列を有するMVAベクター。IMVおよびEEV(上記の方法で調製)を含んでなるロットおよびIMVのみを含んでなるロットの2つのロットを試験した。
6−8週齢のC57BI/6雌マウスを、この研究に用いた。これらのマウスはCharles River(ルーアン,フランス)から入手した。
TC1系を、HPV−16 E6およびE7およびc−Ha−ras癌遺伝子で同時形質転換したC57BI/6マウスの一次肺上皮細胞から誘導した。これらの細胞は、グルタミン(2mM)、ウシ胎仔血清(10%)、非必須アミノ酸(0.1mM)、ピルビン酸Na(1mM)、β−メルカプトエタノール(36μM)、ハイグロマイシン(0.2mg/ml)およびG418(0.5mg/ml)を含むDMEMで増殖する。融解の後、細胞を2回増幅し、最後の継代は細胞の注入の2日前に行った。
実験の第一日目に、TC1細胞をマウスの側腹部に2.0E+05個/マウスの用量で皮下注射した。
細胞注入の7日後、5.0E+05 pfu/50μl/マウスの試験ロット(TG4001 IMV/EEVまたはIMVのみ)およびMVATGN33(エンプティーベクター)をマウスに注入した。20尾のマウスを、試験ロット当たりに用いた。
腫瘍増殖を、カリパスを用いて細胞注入後90日間観察した。腫瘍の大きさが直径が25 mmを越えたときまたは腫瘍が小さめであってもマウスが痛みを示したとき、マウスをエタノールで屠殺した。
生き残っているマウスを、記録した。
HPV抗原をコードするMVAベクターを投与した総ての群は、エンプティーMVAベクターを投与した群より高い生存率を示した。EEVとIMVを含んでなる組成物を投与したマウスは、IMVのみを含んでなる組成物を投与したマウスより高い生存率を示した。更に、EEVとIMVを含んでなる組成物を投与したマウスの35%には注入の77日後に腫瘍は見られず、IMVのみを含んでなる組成物を投与したマウスでは10%に過ぎなかった。
それぞれのベクター構造の名称および簡単な説明
TG4010: MUC1タンパク質(プロモーターp7.5の制御下)およびIL2(プロモーターpH5Rの制御下)のコード配列を有するMVAベクター。IMVおよびEEVを含んでなるロットおよびIMVのみを含んでなるロットの2つのロットを試験した。
種、血統および供給業者: 6〜8週齢のC57BI/6雌マウスを、この研究に用いた。これらのマウスはCharles River(フランス,ルーアン)から入手した。
RMA腫瘍系を、C57BI/6リンパ腫から誘導した。RMA−MUC1細胞は、MUC1遺伝子aを含む発現プラスミドでトランスフェクションした後に得た。これらの細胞を、グルタミン(2mM)、ウシ胎仔血清(10%)、非必須アミノ酸(0.1mM)、ピルビン酸Na(1mM)、β−メルカプトエタノール(36μM)およびハイグロマイシン(550μg/ml)を含むDMEMで増殖した。融解の後、細胞を2回増幅し、最後の継代は抗原投与の前日に行った。
マウスを、TG4010ウイルスに対して1.0x104または3.0x104pfu/マウスおよびMVATGN33に対して3.0x104pfu/マウスで免疫した。
最後の免疫の2週間後、マウスの同じ側腹部にウイルス注入点とは離れた部位に1.0 E+06 RMA−MUC1生存可能な細胞/50μl/マウスを皮下投与した。
腫瘍増殖を、カリパスを用いて腫瘍投与後6週間観察した。腫瘍の大きさが直径が25 mmを越えたときまたは腫瘍が小さめであってもマウスが痛みを示したとき、マウスをエタノールで屠殺した。
MUC1抗原をコードするMVAベクターを投与した総ての群は、エンプティーMVAベクターを投与した群より低い腫瘍増殖と高い生存率を示した。EEVとIMVを含んでなる組成物を投与したマウスは、IMVのみを含んでなる組成物を投与したマウスより低い腫瘍増殖を示した。
Claims (33)
- 組換え修飾ワクシニアウイルスアンカラ(Ankara)(MVA)を含んでなるウイルス粒子組成物の産生方法であって、
前記ウイルス粒子組成物が、標的感染特異性を持たない細胞外エンベロープウイルス(EEV)と、前記組換え修飾ワクシニアウイルスアンカラの細胞内成熟ウイルス(IMV)とを含んでなり、
a) パッケージング細胞の培養物を調製し、
b) 前記細胞培養物を感染させて感染細胞を得、
c) 前記感染細胞を適当な時間培養してウイルス粒子を産生し、かつ
d) 培養物上清およびパッケージング細胞から産生したウイルス粒子を回収する
工程を含んでなり、
前記工程d)がパッケージング細胞を崩壊させる工程を含んでなり、かつ前記ウイルス粒子組成物に含まれる組換えMVAの1%より多くがEEVである、方法。 - 動物産物を含まない、請求項1に記載の方法。
- パッケージング細胞がCEFである、請求項1または2に記載の方法。
- 工程c)が2〜4日間続く、請求項1〜3のいずれか一項に記載の方法。
- 工程d)が高速ホモジナイザーの使用によるパッケージング細胞の崩壊を含んでなる、請求項1〜4のいずれか一項に記載の方法。
- 工程d)から得た混合物を浄化して細胞破片を除去する浄化工程をさらに含んでなる、請求項1〜5のいずれか一項に記載の方法。
- 浄化工程が深層濾過工程である、請求項6に記載の方法。
- 濃縮工程をさらに含んでなる、請求項6または7に記載の方法。
- 濃縮工程が精密濾過工程である、請求項8に記載の方法。
- 透析濾過工程をさらに含んでなる、請求項8に記載の方法。
- ヌクレアーゼ、更に詳細にはベンゾナーゼを用いない、請求項1〜10のいずれか一項に記載の方法。
- 組換えMVAが、直接または間接的細胞傷害性機能を有する分子をコードする外来配列を含んでなる、請求項1〜11のいずれか一項に記載の方法。
- 外来配列が自殺遺伝子である、請求項12に記載の方法。
- 組換えMVAが、腫瘍関連抗原(TAA)をコードする外来配列を含んでなる、請求項1〜11のいずれか一項に記載の方法。
- 組換えMVAが、抗原をコードする外来配列を含んでなる、請求項1〜11のいずれか一項に記載の方法。
- 抗原がウイルスに由来する、請求項15に記載の方法。
- 組換えMVAが、外来配列の発現に必要な要素を含んでなる、請求項1〜16のいずれか一項に記載の方法。
- 請求項1〜17のいずれか一項に記載の方法によって得た組換えMVAを含んでなる、ウイルス粒子組成物。
- 組成物に含まれる組換えMVAの5%より多くがEEVである、請求項18に記載の組成物。
- 組成物に含まれる組換えMVAの10%より多くがEEVである、請求項19に記載の組成物。
- 組成物に含まれる組換えMVAの少なくとも20%がEEVである、請求項20に記載の組成物。
- 力価が、少なくとも105pfu/mlである、請求項18〜21のいずれか一項に記載の組成物。
- 力価が、少なくとも106pfu/mlである、請求項22に記載の組成物。
- 力価が、少なくとも107pfu/mlである、請求項23に記載の組成物。
- 力価が、少なくとも108pfu/mlである、請求項24に記載の組成物。
- 力価が、少なくとも103pfu/μgタンパク質である、請求項18〜25のいずれか一項に記載の組成物。
- 力価が、少なくとも104pfu/μgタンパク質である、請求項26に記載の組成物。
- 力価が、少なくとも3×105pfu/μgタンパク質である、請求項27に記載の組成物。
- 請求項1〜17のいずれか一項に記載の方法によって得た組換えMVA。
- (i) 請求項29に記載の組換えMVA、または
(ii) 請求項18〜28のいずれか一項に記載の組成物
を含んでなる医薬組成物。 - 医薬上許容可能なキャリヤーを含んでなる、請求項30に記載の医薬組成物。
- 癌の治療または予防処置に使用するための、請求項30または31に記載の医薬組成物。
- 感染性疾患の治療または予防処置に使用するための、請求項30または31に記載の医薬組成物。
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TW201321016A (zh) | 2011-09-29 | 2013-06-01 | Transgene Sa | 免疫療法組成物及用於治療c型肝炎病毒感染之療程(二) |
WO2013045658A1 (en) | 2011-09-29 | 2013-04-04 | Transgene Sa | Immunotherapy composition and regimen for treating hepatitis c virus infection |
TWI690322B (zh) | 2012-10-02 | 2020-04-11 | 法商傳斯堅公司 | 含病毒的調配物及其使用 |
ES2909957T3 (es) | 2014-07-16 | 2022-05-11 | Transgene | Virus oncolítico para la expresión de moduladores de puntos de control inmunitarios |
CN104147145B (zh) * | 2014-07-31 | 2017-01-11 | 许峰 | 一种预防和治疗羊痘的药剂 |
DK3226894T3 (da) | 2014-12-01 | 2019-10-21 | Transgene Sa | Stabile flydende vacciniavirus-formuleringer |
WO2016131945A1 (en) | 2015-02-20 | 2016-08-25 | Transgene Sa | Combination product with autophagy modulator |
CN106591361A (zh) * | 2015-10-20 | 2017-04-26 | 钱文斌 | 一种重组痘溶瘤病毒及其构建方法和应用 |
EP3402802B1 (en) * | 2016-01-08 | 2023-04-12 | Geovax, Inc. | Compositions and methods for generating an immune response to a tumor associated antigen |
US20190134190A1 (en) | 2016-05-04 | 2019-05-09 | Transgene Sa | Combination therapy with cpg tlr9 ligand |
EP3522920A2 (en) | 2016-10-10 | 2019-08-14 | Transgene SA | Immunotherapeutic product and mdsc modulator combination therapy |
WO2018091680A1 (en) | 2016-11-18 | 2018-05-24 | Transgene Sa | Cowpox-based oncolytic vectors |
ES2905478T3 (es) | 2016-12-28 | 2022-04-08 | Transgene Sa | Virus oncolíticos y moléculas terapéuticas |
US11306292B2 (en) | 2017-05-15 | 2022-04-19 | Janssen Vaccines & Prevention B.V. | Stable virus-containing composition |
WO2018211419A1 (en) | 2017-05-15 | 2018-11-22 | Janssen Vaccines & Prevention B.V. | Stable virus-containing composition |
SG11201912429RA (en) * | 2017-06-21 | 2020-01-30 | Transgene Sa | Personalized vaccine |
WO2019020543A1 (en) | 2017-07-28 | 2019-01-31 | Transgene Sa | ONCOLYTIC VIRUSES EXPRESSING AGENTS TARGETING METABOLIC IMMUNE MODULATORS |
KR20200121297A (ko) | 2018-01-05 | 2020-10-23 | 오타와 하스피털 리서치 인스티튜트 | 변형된 오르토폭스바이러스 벡터 |
AU2019208892B2 (en) * | 2018-01-19 | 2022-02-03 | Kolon Life Science, Inc. | Recombinant vaccinia virus and pharmaceutical composition comprising same |
CN112512560A (zh) | 2018-03-07 | 2021-03-16 | 特兰斯吉恩股份有限公司 | 副痘病毒属载体 |
WO2020011754A1 (en) | 2018-07-09 | 2020-01-16 | Transgene | Chimeric vaccinia viruses |
EP3617230A1 (en) | 2018-09-03 | 2020-03-04 | BioInvent International AB | Novel antibodies and nucleotide sequences, and uses thereof |
JP7437385B2 (ja) | 2018-09-06 | 2024-02-22 | バヴァリアン・ノルディック・アクティーゼルスカブ | 保管が改善されたポックスウイルス組成物 |
AU2019412516A1 (en) | 2018-12-28 | 2021-07-15 | Transgene | M2-defective poxvirus |
EP3842065A1 (en) | 2019-12-23 | 2021-06-30 | Transgene | Process for designing a recombinant poxvirus for a therapeutic vaccine |
AU2021233167A1 (en) | 2020-03-12 | 2022-09-22 | Bavarian Nordic A/S | Compositions improving poxvirus stability |
JP2023533584A (ja) | 2020-07-13 | 2023-08-03 | トランジェーヌ | 免疫低下の処置 |
WO2022148736A1 (en) | 2021-01-05 | 2022-07-14 | Transgene | Vectorization of muc1 t cell engager |
WO2023025899A2 (en) | 2021-08-26 | 2023-03-02 | Transgene | Delivery system for targeting genes of the interferon pathway |
TW202321458A (zh) | 2021-09-22 | 2023-06-01 | 瑞典商生物創新國際公司 | 新穎抗體組合及其用途 |
WO2023128672A1 (ko) * | 2021-12-29 | 2023-07-06 | 재단법인 아산사회복지재단 | 외피외 바이러스 생산이 증가한 신규한 백시니아 바이러스 변이주 |
WO2023213763A1 (en) | 2022-05-02 | 2023-11-09 | Transgene | Poxvirus encoding a binding agent comprising an anti- pd-l1 sdab |
WO2023213764A1 (en) | 2022-05-02 | 2023-11-09 | Transgene | Fusion polypeptide comprising an anti-pd-l1 sdab and a member of the tnfsf |
WO2023238106A1 (en) | 2022-06-10 | 2023-12-14 | Transgene | Recombinant virus expressing interleukin-12 |
WO2024003239A1 (en) | 2022-06-29 | 2024-01-04 | Bavarian Nordic A/S | RECOMBINANT MODIFIED saRNA (VRP) AND VACCINIA VIRUS ANKARA (MVA) PRIME-BOOST REGIMEN |
WO2024003238A1 (en) | 2022-06-29 | 2024-01-04 | Bavarian Nordic A/S | Epstein-barr-virus vaccine |
WO2024003353A1 (en) | 2022-07-01 | 2024-01-04 | Transgene | Fusion protein comprising a surfactant-protein-d and a member of the tnfsf |
WO2024023740A1 (en) | 2022-07-27 | 2024-02-01 | Astrazeneca Ab | Combinations of recombinant virus expressing interleukin-12 with pd-1/pd-l1 inhibitors |
WO2024038175A1 (en) | 2022-08-18 | 2024-02-22 | Transgene | Chimeric poxviruses |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4675187A (en) | 1983-05-16 | 1987-06-23 | Bristol-Myers Company | BBM-1675, a new antibiotic complex |
GB8705477D0 (en) | 1987-03-09 | 1987-04-15 | Carlton Med Prod | Drug delivery systems |
GB9001641D0 (en) | 1990-01-24 | 1990-03-21 | Imp Cancer Res Tech | Compounds |
GB9208402D0 (en) | 1992-04-16 | 1992-06-03 | Devro Ltd | Rotatable linking and hanging device |
ATE322547T1 (de) | 1993-06-10 | 2006-04-15 | Genetic Therapy Inc | Adenovirale vektoren für die behandlung der hämophilie |
UA68327C2 (en) * | 1995-07-04 | 2004-08-16 | Gsf Forschungszentrum Fur Unwe | A recombinant mva virus, an isolated eukaryotic cell, infected with recombinant mva virus, a method for production in vitro of polypeptides with use of said cell, a method for production in vitro of virus parts (variants), vaccine containing the recombinant mva virus, a method for immunization of animals |
FR2751879B1 (fr) * | 1996-07-30 | 1998-10-30 | Transgene Sa | Composition pharmaceutique contre les tumeurs et infections a papillomavirus |
US7118754B1 (en) | 1996-07-30 | 2006-10-10 | Transgene S.A. | Pharmaceutical composition for treating papillomavirus tumors and infection |
US5672485A (en) | 1996-08-13 | 1997-09-30 | Regents Of The University Of Minnesota | Immortalized cell lines for virus growth |
FR2766091A1 (fr) * | 1997-07-18 | 1999-01-22 | Transgene Sa | Composition antitumorale a base de polypeptide immunogene de localisation cellulaire modifiee |
FR2777570A1 (fr) | 1998-04-17 | 1999-10-22 | Transgene Sa | Mutant ayant une activite phosphoribosyl transferase |
US7348014B2 (en) * | 2000-04-14 | 2008-03-25 | Transgene, S.A. | Poxvirus with targeted infection specificity |
DE60116371T3 (de) * | 2000-11-23 | 2016-11-17 | Bavarian Nordic A/S | Variante des modifizierten vaccinia ankara virus |
DE10143490C2 (de) * | 2001-09-05 | 2003-12-11 | Gsf Forschungszentrum Umwelt | Rekombinantes MVA mit der Fähigkeit zur Expression von HCV Struktur-Antigenen |
KR20120002613A (ko) * | 2002-08-12 | 2012-01-06 | 제네렉스, 인코포레이티드 | 폭스바이러스 및 암과 관련된 방법 및 조성물 |
EP1434858B2 (en) * | 2002-09-05 | 2018-12-19 | Bavarian Nordic A/S | Method for the amplification of a poxvirus under serum free conditions |
PT1649023E (pt) | 2003-07-21 | 2008-11-20 | Transgene Sa | Polipéptido com actividade de citosina desaminase melhorada |
DK1646715T3 (da) | 2003-07-22 | 2010-08-16 | Vivalis | Fremstilling af poxvirum med adhærente eller ikke-adhærente fuglecellelinjer |
US20060094104A1 (en) | 2004-10-29 | 2006-05-04 | Leopold Grillberger | Animal protein-free media for cultivation of cells |
EP1807508A4 (en) * | 2004-11-05 | 2008-03-12 | Us Gov Health & Human Serv | METHODS FOR PREPARING CELLS AND VIRUSES |
US8058049B2 (en) * | 2006-06-20 | 2011-11-15 | Transgene S.A. | Process for producing poxviruses and poxvirus compositions |
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