JP2021504293A - インターフェロン感受性ウイルスの産生、増殖、拡散または腫瘍溶解性および免疫治療の効果を高めるための組成物およびその方法。 - Google Patents
インターフェロン感受性ウイルスの産生、増殖、拡散または腫瘍溶解性および免疫治療の効果を高めるための組成物およびその方法。 Download PDFInfo
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Abstract
Description
使用したqPCRプライマーのリスト:
gapdh (For -ACAGTCAGCCGCATCTTCTT (SEQ ID NO: 1); Rev-
GTTAAAAGCAGCCCTGGTGA) (SEQ ID NO:2)
hmox1 (For-ACTGCGTTCCTGCTCAACAT (SEQ ID NO:3); Rev-
GGGGCAGAATCTTGCACTTT) (SEQ ID NO:4)
nrf2 (For-CAACTACTCCCAGGTTGCCC (SEQ ID NO:5); Rev-
AGTGACTGAAACGTAGCCGA) (SEQ ID NO:6)
ifitm1 (For-CCGTGAAGTCTAGGGACAGG (SEQ ID NO:7); Rev-
GGTAGACTGTCACAGAGCCG) (SEQ ID NO:8)
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Claims (18)
- 不死化細胞、がん細胞、または腫瘍細胞におけるインターフェロン感受性ウイルスの産生、感染、増殖、拡散、または力価を高める方法であり、前記方法は不死化細胞、がん細胞、腫瘍細胞にインターフェロン感受性ウイルスを感染させる前に、同時にまたは後にフマル酸エステルおよびマレイン酸エステル(FMAE)含有化合物またはその誘導体を不死化細胞、がん細胞または腫瘍細胞に投与することを特徴とする前記方法。
- 前記インターフェロン感受性ウイルスは遺伝的にインターフェロン感受性にした非インターフェロン感受性ウイルス、弱毒化インターフェロン感受性ウイルス、インターフェロン感受性腫瘍溶解性ウイルス、または非複製インターフェロン感受性ウイルスであることを特徴とする、請求項1に記載の方法。
- 前記インターフェロン感受性腫瘍溶解性ウイルスは、がん細胞または腫瘍細胞において腫瘍溶解活性、細胞死活性、および/または傷害活性を高めるまたは増加することを特徴とする、請求項2に記載の方法。
- 前記インターフェロン感受性腫瘍溶解性ウイルスは、がん細胞または腫瘍細胞において免疫治療活性を高める、増加または強化し、ウイルスにエンコードされたトランスジーンおよび/またはサイトカインのアップレギュレーションを含むことを特徴とする、請求項2に記載の方法。
- 前記FMAE含有化合物が、フマル酸ジメチル(DMF)、フマル酸ジエチル(DEF)、マレイン酸ジメチル(DMM)、マレイン酸ジエチル(DEM)、マレイン酸モノエチル、マレイン酸モノメチル、フマル酸モノエチル、またはフマル酸モノメチル(MMF)の構造である、またはその構造を含み、薬学的に許容されるその塩、溶媒和物、水和物、プロドラッグ、還元、または酸化型を含むことを特徴とする、請求項1に記載の方法。
- 上記インターフェロン感受性ウイルスが、レオウイルス、ニューカッスル病ウイルス、ポリオウイルス、ムンプスウイルス、麻疹ウイルス、インフルエンザウイルス、マラバウイルス(MG−1のような)、狂犬病ウイルス、ロタウイルス、A型肝炎ウイルス、風疹ウイルス、デングウイルス、アデノウイルス、単純ヘルペスウイルス、またはラブドウイルス、またはその変異型または派生型であることを特徴とする、請求項1に記載の方法。
- 前記インターフェロン感受性腫瘍溶解性ウイルスは、水疱性口内炎ウイルスまたはその派生型または変異体であるラブドウイルスを含むことを特徴とする、請求項2に記載の方法
- 前記インターフェロン感受性ウイルスが、組み換え技術を用いた遺伝子改変、またはそれらの任意の組み合わせの一つ以上の選択圧さらされる、特異的な増殖条件下でウイルスが選択されることを含むことを特徴とする、請求項1に記載の方法。
- 前記細胞が哺乳類細胞であることを特徴とする、請求項1に記載の方法。
- 前記細胞がヒト細胞であることを特徴とする、請求項9に記載の方法。
- 前記不死化細胞、がん細胞、または腫瘍細胞が293−T細胞,BHK21細胞,またはMDCK細胞,Vero細胞,HEK−293細胞,EB−66細胞,EB−bX細胞,PER−.C6細胞,AGE1.CR細胞,Agel.CS細胞,Agel.HN細胞,Agel.RO細胞,QOR2/2E11細胞,UMNSAH−DF1細胞,CHO細胞,hybridoma細胞,sf9細胞,またはR4細胞であり、293−T細胞、BHK21細胞、またはMDCK細胞がリンパ芽球性白血病、骨髄性白血病、副腎皮質がん、AIDS関連がん、AIDS関連リンパ腫、肛門がん、虫垂がん、星細胞腫、奇形腫様/ラブドイド腫瘍、基底細胞がん、胆管がん、膀胱がん、骨がん、骨肉腫、悪性線維性組織球腫、脳幹神経膠腫、脳腫瘍、小脳星細胞腫、脳星細胞腫/悪性神経膠腫、頭蓋咽頭腫、上衣芽腫、髄芽腫、中間分化の松果体実質腫瘍、テント上原始神経外胚葉腫瘍および松果体芽腫、視覚経路および視床下部神経膠腫、脊髄腫瘍、乳癌、気管支腫瘍、バーキットリンパ腫、カルチノイド腫瘍、中枢神経系リンパ腫、子宮頸がん、脊索腫、慢性リンパ性白血病、慢性骨髄性白血病、慢性骨髄増殖性疾患、結腸がん、皮膚T細胞リンパ腫、胚性腫瘍、子宮内膜がん、上衣芽腫、上衣腫、食道がん、頭蓋外胚細胞腫瘍、性腺外胚細胞腫瘍、肝外胆管がん、眼がん、眼内黒色腫、網膜芽細胞腫、胆嚢がん、胃(胃)がん、胃腸カルチノイド腫瘍、消化管間質腫瘍(GIST)、消化管間質細胞腫瘍、胚細胞腫瘍、頭蓋外、外性、卵巣、妊娠性絨毛腫瘍、神経膠腫、有毛細胞白血病、頭頸部がん、肝細胞(肝臓)がん、組織球症、ランゲルハンス細胞がん、ホジキンリンパ腫、下咽頭がん、膵島細胞腫瘍、カポジ肉腫、腎臓がん、喉頭がん、リンパ球性白血病、毛様細胞白血病、唇および口腔がん、肝臓がん、非小細胞肺がん、小細胞肺がん、ホジキンリンパ腫、非ホジキンリンパ腫、骨および骨肉腫の悪性線維性組織球腫、髄芽腫、髄上皮腫、黒色腫、眼内黒色腫、メルケル細胞癌、中皮腫、転移性扁平上皮癌、口腔癌、多発性内分泌腫瘍症候群、多発性骨髄腫/形質細胞腫瘍、鼻腔および副鼻腔がん、鼻咽頭がん、神経芽細胞腫、口腔がん、口腔咽頭がん、卵巣がん、膵臓がん、副甲状腺がん、陰茎がん、咽頭がん、褐色細胞腫、松果体実質腫瘍、松果体芽腫および上原始神経外胚葉性腫瘍、下垂体腫瘍、形質細胞腫瘍/多発性骨髄腫、胸膜肺芽腫、原発性中枢神経系リンパ腫、前立腺がん、直腸がん、腎細胞(腎臓)がん、腎および尿管がん、移行上皮がん、気道がん、網膜芽細胞腫、横紋筋肉腫、唾液腺がん、子宮肉腫、皮膚がん、メルケル細胞がん、小腸がん、軟部肉腫、扁平上皮がん、扁平上皮がん、胃(胃)がん、テント上、原始神経外胚葉性腫瘍、T細胞リンパ腫、精巣がん、咽頭がん、胸腺がん、胸腺がん、甲状腺がん、栄養芽腫、尿道がん、子宮がん、子宮内膜がん、子宮肉腫、膣がん、外陰がん、またはウィルムス腫瘍を含むことを特徴とする、請求項1記載の方法。
- それを必要とする対象の腫瘍またはがんを治療する方法であって、
対象にインターフェロン感受性ウイルスを投与する前、した後、またはそれと同時に、対象にフマル酸エステルおよびマレイン酸エステル(FMAE)含有化合物またはそれらの誘導体を投与することを含むことを特徴とする上記方法。 - 少なくとも一つのフマル酸エステルおよびマレイン酸エステル(FMAE)含有化合物またはそれらの誘導体、または薬学的に許容されるキャリアまたは賦形剤を含む組成物であって、ウイルス増強に用いることを特徴とする組成物。
- インターフェロン感受性ウイルスおよび少なくとも一つのフマル酸エステルおよびマレイン酸エステル(FMAE)含有化合物、またはその誘導体を含むことを特徴とする組成物。
- インターフェロン感受性ウイルスを産生する方法であって、
少なくともフマル酸エステルおよびマレイン酸エステル(FMAE)含有化合物またはその誘導体存在下で、適切な溶媒で、インターフェロン感受性ウイルスまたはその成分と不死化細胞、がん細胞、または腫瘍細胞を培養すること、および、
その不死化細胞、がん細胞、腫瘍細胞からインターフェロン感受性ウイルスを産生すること、を含むことを特徴とする前記方法。 - 上記インターフェロン感受性ウイルスが、弱毒化ウイルス、遺伝子改変ウイルス、非複製ウイルス、または腫瘍溶解性ウイルスであることを特徴とする、請求項15に記載の方法。
- 上記インターフェロン感受性ウイルスが、がんワクチンを調製するために用いられるものであって、ウイルスがワクチンであるまたはワクチンがウイルスに感染した細胞を含むことを特徴とする請求項16に記載の方法。
- 上記産生されたウイルスがインターフェロン感受性ウイルスベースの遺伝子治療ベクターであることを特徴とする、請求項16に記載の方法。
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