JP5492986B2 - パルボウイルスおよびサイトカインの共投与に基づいた癌治療のための方法 - Google Patents
パルボウイルスおよびサイトカインの共投与に基づいた癌治療のための方法 Download PDFInfo
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
- A61K35/768—Oncolytic viruses not provided for in groups A61K35/761 - A61K35/766
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- A61K38/00—Medicinal preparations containing peptides
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/217—IFN-gamma
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C12N2750/14011—Parvoviridae
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Description
(a) インターフェロンI型:ヒトに存在するI型インターフェロンは、IFN-α、IFN-βおよびIFN-ωである。
(b) インターフェロンII型:ヒトにおいて、これはIFN-γである。
(c) インターフェロンIII型:IL10R2(CRF2-4とも称される)およびIFNLR1(CRF2-12とも称される)からなるレセプター複合体を介したシグナル。
材料および方法
(A) ウイルス生成および検出
野生型H-1ウイルスを、NBK細胞に感染させて生成し、イオジキサノール勾配遠心分離により精製し、リンガー溶液に対して透析した。複製中心形成単位(cfu)として以前に記載され、表現されるようにウイルス力価を測定した。簡潔に、精製したウイルスの連続希釈液をNBK細胞に適用した。感染後48時間で、感染培養物をフィルターにブロットして、ウイルスDNA特異的放射性プローブを使用して、ハイブリダイゼーションにより複製中心を検出した(Russell et al., J Virol 1992;66:2821-8)。
(i) 麻酔. 全ての外科的手順および画像化手順は、純粋酸素中のイソフルラン(Aerrane(登録商標), Baxter, Maurepas, France)を用いる気体麻酔下で行なった。イソフルラン濃度は、麻酔の開始時に5%から、外科的手順または画像化手順の間は2% (+/-0.5%)で変えた。
0.4mlの造影剤(ガドジアミド、OmniscanTM, Amersham, Braunschweig, Germany)の尾静脈への注射の前後にT1加重画像法(weighted imaging)を使用して、2.45テスラMRIスキャナ(Bruker, Ettlingen, Germany)中で動物を調べた。注射の5分後にガドジアミド増強T1画像法を行なった。MR試験中、イソフルラン吹込み(開始用量5%、維持2%)によりラットを麻酔した。MRIcroソフトウェアを使用して腫瘍の体積を測定した。
IFN-γとパルボウイルスH-1(H-1PV)を合わせることによる、免疫応答性ラット中のラット神経膠腫の治療有効性の増加
腫瘍モデル:ラット神経膠腫細胞株の細胞(RG2細胞)を、Wistarラットの右前脳に、頭蓋内に埋め込んだ(動物あたり104細胞)。全部で11匹の免疫応答性Wistarラット(6〜7週齢、240〜250g、雌)を該実験で分析した。
結果を図1に示す。
IFN-γとパルボウイルスH-1(H-1PV)を合わせることによる、免疫不全ラットにおけるヒト神経膠腫細胞株由来脳腫瘍の治療有効性の増加
腫瘍モデル:ヒト神経膠腫細胞株の細胞(U87細胞)を、ラットの右前脳に、頭蓋内に埋め込んだ(動物あたり105細胞)。該実験において、全部で18匹の免疫不全RNUラット(6〜7週齢、220〜250g、雌)を分析した。
結果を図2に示す。
Claims (5)
- 癌の治療用医薬組成物の調製のための、パルボウイルスH-1(H1-PV)およびIFN-γの使用であって、(a)パルボウイルスH-1および(b)IFN-γは、連続的に投与されるか、または一緒に投与される、使用。
- 前記癌が脳腫瘍である、請求項1記載の使用。
- 前記脳腫瘍が、神経膠腫、髄芽腫または髄膜腫である、請求項2記載の使用。
- 前記神経膠腫が、悪性ヒト神経膠芽腫である、請求項3記載の使用。
- 前記パルボウイルスH-1が腫瘍内投与により投与される、請求項1〜4いずれか記載の使用。
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