JP2018534357A - がんを予防又は治療する方法及び組成物 - Google Patents
がんを予防又は治療する方法及び組成物 Download PDFInfo
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Abstract
Description
本明細書と同時に提出され、2016年10月6日に作成された、184,774バイトASCII(テキスト)のファイルネーム「026389−9173_ST25.txt」として識別される、コンピューター読み取り可能ヌクレオチド/アミノ酸配列表を、参照により本明細書にその全体を組み込む。
本開示は、がん細胞を、(a)それぞれがゾウp53タンパク質をコードする1つ以上の核酸配列又は(b)1つ以上のゾウp53タンパク質と接触させることを含み、これによりがんが阻害される、がんを阻害する方法を提供する。
本開示は、がん細胞を、それぞれが1つのゾウp53タンパク質、又は1つ以上のゾウp53タンパク質をコードする1つ以上の核酸配列と接触させることを含む、がんを阻害する方法を提供する。
特定の実施形態では、1つ以上のゾウp53タンパク質をコードする1つ以上のゾウTP53核酸配列は、組成物の形態にある。したがって、本開示は、医薬として許容される担体、及び(a)それぞれがゾウp53タンパク質をコードする1つ以上の核酸配列、又は(b)1つ以上のゾウp53タンパク質を含む組成物も提供する。任意の適する医薬として許容される担体は、本開示の文脈において利用可能であり、またそのような担体は、当技術分野において周知されている。担体の選択は、組成物が投与される特定の部位、及び組成物の投与に使用される特定の方法により、一部決定される。組成物のための代表的な処方物として、経口処方物、注入用処方物、及びエアゾール処方物が挙げられるが、これらに限定されない。
本開示は、それぞれが本明細書に記載するゾウp53タンパク質をコードする1つ以上の核酸配列、本明細書に記載する1つ以上のゾウp53タンパク質又は1つ以上の本明細書に記載するゾウ核酸配列タンパク質を含む組成物を使用して、がんを阻害する方法を提供する。用語「がんを阻害すること」とは、本明細書で用いる場合、1つ以上のがん細胞の成長、増殖及び/又は転移を予防、抑制、ブロックし、又は低速化させることを意味する。いくつかの実施形態では、例えば本明細書に記載する方法は、がん細胞の増殖阻害、がん細胞の血管新生阻害、がん細胞の根絶及び/又は少なくとも1つのがん性腫瘍のサイズの縮小を促進し得、それにより、ヒトががんについて治療される。
この実施例は、体重ががんの罹病率と相関関係を有するか、その真否を確認するために、異なる哺乳動物種(ゾウを含む)のがん発生率について記載する。
この実施例は、ゾウにおけるがん関連遺伝子のゲノム分析について記載する。
この実施例は、ヒト細胞株内にトランスフェクトされたゾウEP53レトロ遺伝子が、タンパク質に翻訳され得たことを実証する。
この実施例は、ゾウ及びヒトの末梢血リンパ球中における細胞のDNA損傷に対する応答について記載する。
この実施例は、EP53発現が、様々なEP53遺伝子でトランスフェクトしたヒトがん細胞株U−2OS(骨肉腫)のアポトーシスを増加させることができるかどうかについて評価する。
Claims (49)
- がんを阻害する方法であって、
がん細胞を
(a)それぞれがゾウp53タンパク質をコードする1つ以上の核酸配列、又は
(b)1つ以上のゾウp53タンパク質
と接触させることを含み、これによりがんが阻害される方法。 - がん細胞を、それぞれがゾウp53タンパク質をコードする1つ以上の核酸配列と接触させることを含む、請求項1に記載の方法。
- ゾウp53タンパク質をコードする核酸配列が、レトロ遺伝子である、請求項2に記載の方法。
- ゾウp53タンパク質をコードする核酸配列が、祖先遺伝子である、請求項2に記載の方法。
- がん細胞を、それぞれがゾウp53タンパク質をコードする複数の核酸配列と接触させることを含む、請求項2に記載の方法。
- 複数の核酸配列が、複数の異なるレトロ遺伝子を含む、請求項5に記載の方法。
- 複数の核酸配列のうちの少なくとも1つが、祖先遺伝子を含む、請求項6に記載の方法。
- 1つ以上の核酸配列が、RNA又はDNAを含む、請求項1〜7のいずれか一項に記載の方法。
- レトロ遺伝子が、配列番号4、配列番号6、配列番号8、配列番号10、配列番号12、配列番号14、配列番号16、配列番号18、配列番号20、配列番号22、配列番号24、配列番号26、配列番号28、配列番号30、配列番号32、配列番号34、配列番号36、配列番号38、配列番号40、配列番号42、配列番号44、配列番号46、配列番号48、配列番号50、配列番号52、配列番号54、配列番号56、配列番号58、配列番号60、配列番号62、配列番号64、配列番号66、配列番号68、配列番号70、配列番号72、配列番号74、又は配列番号76
の核酸配列を含む、請求項3又は請求項6に記載の方法。 - 祖先遺伝子が、配列番号2の核酸配列を含む、請求項4又は請求項7に記載の方法。
- がん細胞を、1つ以上のゾウp53タンパク質と接触させることを含む、請求項1に記載の方法。
- がん細胞を、1つのゾウp53タンパク質と接触させることを含む、請求項11に記載の方法。
- ゾウp53タンパク質が、レトロ遺伝子によりコードされる、請求項12に記載の方法。
- ゾウp53タンパク質が、祖先遺伝子によりコードされる、請求項13に記載の方法。
- がん細胞を、複数の異なるゾウp53タンパク質と接触させることを含む、請求項11に記載の方法。
- 複数の異なるゾウp53タンパク質が、複数の異なるレトロ遺伝子によりコードされる、請求項15に記載の方法。
- 複数の異なるゾウp53タンパク質のうちの少なくとも1つが、祖先p53タンパク質である、請求項16に記載の方法。
- P53タンパク質が、配列番号5、配列番号7、配列番号9、配列番号11、配列番号13、配列番号15、配列番号17、配列番号19、配列番号21、配列番号23、配列番号25、配列番号27、配列番号29、配列番号31、配列番号33、配列番号35、配列番号37、配列番号39、配列番号41、配列番号43、配列番号45、配列番号47、配列番号49、配列番号51、配列番号53、配列番号55、配列番号57、配列番号59、配列番号61、配列番号63、配列番号65、配列番号67、配列番号69、配列番号71、配列番号73、配列番号75、及び配列番号77
のアミノ酸配列を含む、請求項13又は請求項16に記載の方法。 - p53タンパク質が、配列番号3のアミノ酸配列を含む、請求項14又は請求項17に記載の方法。
- 1つ以上の核酸配列又は1つ以上のゾウp53タンパク質が、医薬として許容される担体を含む組成物の形態にある、請求項1〜19のいずれか一項に記載の方法。
- 組成物が、リポソームを含む、請求項20に記載の方法。
- 1つ以上の核酸配列又は1つ以上のp53タンパク質が、リポソーム内にカプセル化されている、請求項21に記載の方法。
- 組成物が、ナノ粒子を含む、請求項20に記載の方法。
- ナノ粒子が、有機物質、無機物質、脂質、ポリマー、金属及び炭素ナノ構造体からなる群から選択される1つ以上の充填剤を含む、請求項23に記載の方法。
- ナノ粒子が、リポソーム内にカプセル化されたゾウp53タンパク質又はゾウTP53核酸を含む、請求項23又は24に記載の方法。
- ナノ粒子が、細網内皮系との相互作用を低減する部分で装飾された外部表面を含む、請求項23〜25のいずれか一項に記載の方法。
- 前記部分が、ポリエチレングリコールを含む、請求項26に記載の方法。
- 前記部分が、標的部分を含む、請求項26に記載の方法。
- 標的部分が、がん細胞に対するナノ粒子の親和性を増加させる、請求項28に記載の方法。
- 組成物が、小分子化学療法薬、モノクロナール抗体及びイメージング剤からなる群から選択される1つ以上の添加剤をさらに含む、請求項20〜29のいずれか一項に記載の方法。
- イメージング剤が、造影剤、糖、鉄錯体又はガドリニウム(Gd)を含む、請求項30に記載の方法。
- がん細胞が、インビトロ又はインビボにある、請求項1〜31のいずれか一項に記載の方法。
- がん細胞が、哺乳動物に由来する、請求項1〜32のいずれか一項に記載の方法。
- 哺乳動物が、ヒトである、請求項33に記載の方法。
- 医薬として許容される担体及び
(a)それぞれがゾウp53タンパク質をコードする1つ以上の核酸配列、又は
(b)1つ以上のゾウp53タンパク質
を含む組成物。 - それぞれがゾウp53タンパク質をコードする1つ以上の核酸配列を含む、請求項34に記載の組成物。
- 1つ以上の核酸配列が、RNA又はDNAを含む、請求項34又は35に記載の組成物。
- 1つ以上のゾウp53タンパク質を含む、請求項34に記載の組成物。
- リポソームを含む、請求項34に記載の組成物。
- 1つ以上の核酸配列又は1つ以上のP53タンパク質が、リポソーム内にカプセル化されている、請求項38に記載の組成物。
- ナノ粒子を含む、請求項34に記載の組成物。
- ナノ粒子が、有機物質、無機物質、脂質、ポリマー、金属及び炭素ナノ構造体からなる群から選択される1つ以上の充填剤を含む、請求項40に記載の組成物。
- 1つ以上の核酸配列又は1つ以上のp53タンパク質が、リポソーム内にカプセル化されている、請求項40又は請求項41に記載の組成物。
- ナノ粒子が、細網内皮系との相互作用を低減する部分で装飾された外部表面を含む、請求項40〜42のいずれか一項に記載の組成物。
- 前記部分が、ポリエチレングリコールを含む、請求項43に記載の組成物。
- 前記部分が、標的部分を含む、請求項43に記載の組成物。
- 標的部分が、がん細胞に対するナノ粒子の親和性を増加させる、請求項45に記載の組成物。
- 小分子化学療法薬、モノクロナール抗体、及びイメージング剤からなる群から選択される1つ以上の添加剤をさらに含む、請求項34〜46のいずれか一項に記載の組成物。
- イメージング剤が、造影剤、糖、鉄錯体又はガドリニウム(Gd)を含む、請求項47に記載の組成物。
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