JP2017517260A - Mage−a3ペプチド標的アプタマー及びその使用 - Google Patents
Mage−a3ペプチド標的アプタマー及びその使用 Download PDFInfo
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- JP2017517260A JP2017517260A JP2016569074A JP2016569074A JP2017517260A JP 2017517260 A JP2017517260 A JP 2017517260A JP 2016569074 A JP2016569074 A JP 2016569074A JP 2016569074 A JP2016569074 A JP 2016569074A JP 2017517260 A JP2017517260 A JP 2017517260A
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- Prior art keywords
- cancer
- oligonucleotide aptamer
- seq
- sequence
- peptide
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- 108091023037 Aptamer Proteins 0.000 title claims abstract description 145
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 99
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Abstract
Description
数値は、50,000個のうちGFP陽性又はGFP及びCy3ともに陽性であったカウントの割合を示す。実験を独立して2回実施した平均値を示す。
1数値は、試験培地中に残留するアプタマーの割合を経時的に示す。実験を独立して2回実施した平均値を示す。
2ThioAp52=ホスホロチオエート修飾Ap52。Cy3-Ap52及びCy3-ThioAp52は、Ap52又はThioAp52にCy3を結合させたものを示す。
Claims (39)
- 主要組織適合性複合体(MHC)により細胞表面に提示されたペプチドを標的とするオリゴヌクレオチドアプタマーであって、配列番号1の配列を有するオリゴヌクレオチドアプタマー。
- 前記ペプチドが黒色腫関連抗原A3(MAGE-A3)に由来する、請求項1に記載のオリゴヌクレオチドアプタマー。
- 前記ペプチドが配列番号4のアミノ酸配列を有する、請求項2に記載のオリゴヌクレオチドアプタマー。
- 前記配列番号1の配列の上流及び下流にそれぞれ配列番号2の配列及び配列番号3の配列をさらに有し、前記配列番号2の配列及び前記配列番号3の配列が前記配列番号1の配列の上流及び下流にそれぞれ連結して位置する、請求項1に記載のオリゴヌクレオチドアプタマー。
- 前記細胞が、黒色腫、白血病、舌癌、大腸癌、食道癌、胃癌、肺がん、多発性骨髄腫、膀胱がん、乳がん、膵がん、腎がん、肝細胞癌、卵巣がん、前立腺がん、及び頭頸部扁平上皮癌からなる群より選択される腫瘍に由来する、請求項1に記載のオリゴヌクレオチドアプタマー。
- 前記オリゴヌクレオチドアプタマーが、2'-アミノピリミジニル基、2'-O-メチルプリニル基、5'-ジアルキル基、ホスホロチオエートキャップ、2'-OHヌクレオチド、2'-フルオロピリミジン、又は5-(1-ペンチニル)-2'-デオキシウリジンのうち1種以上の化学基で修飾されている、請求項1に記載のオリゴヌクレオチドアプタマー。
- 前記オリゴヌクレオチドアプタマーがホスホロチオエートキャップで修飾されている、請求項6に記載のオリゴヌクレオチドアプタマー。
- 前記オリゴヌクレオチドアプタマーが蛍光色素、レポーター分子、造影剤、抗がん剤、ペプチド、又は粒子のいずれかに結合している、請求項1に記載のオリゴヌクレオチドアプタマー。
- 前記粒子が酸化鉄磁性粒子である、請求項8に記載のオリゴヌクレオチドアプタマー。
- 前記オリゴヌクレオチドアプタマーが蛍光色素に結合している、請求項8に記載のオリゴヌクレオチドアプタマー。
- 抗腫瘍剤をさらに有し、前記抗腫瘍剤と結合している、請求項1に記載のオリゴヌクレオチドアプタマー。
- 前記抗腫瘍剤がメクロレタミン、シクロホスファミド、メルファラン、クロラムブチル、イホスファミド、ブスルファン、N-ニトロソ-N-メチル尿素、カルムスチン、ロムスチン、セムスチン、ホテムスチン、ストレプトゾトシン、ダカルバジン、ミトゾロミド、テモゾロミド、チオテパ、マイトマイシン、ジアジクオン、シスプラチン、カルボプラチン、オキサリプラチン、メトトレキサート、ペメトレキセド、フルオロウラシル、カペシタビン、シタラビン、ゲムシタビン、デシタビン、ビダーザ、フルダラビン、ネララビン、クラドリビン、クロファラビン、ペントスタチン、チオグアニン、メルカプトプリン、ビンカアルカロイド、タキサン、イリノテカン、トポテカン、エトポシド、ドキソルビシン、ミトキサントロン、テニポシド、ノボビオシン、メルバロン、アクラルビシン、アントラサイクリン、アクチノマイシン、ブレオマイシン、プリカマイシン、又はマイトマイシンのいずれかである、請求項11に記載のオリゴヌクレオチドアプタマー。
- MHCにより細胞表面にペプチドが提示された細胞を標的とする組成物であって、請求項1に記載のオリゴヌクレオチドアプタマー及び薬学的に許容される添加剤を含有する組成物。
- 前記ペプチドがMAGE-A3に由来する、請求項13に記載の組成物。
- 前記ペプチドが配列番号4のアミノ酸配列を有する、請求項14に記載の組成物。
- 前記オリゴヌクレオチドアプタマーが、配列番号1の配列の上流及び下流にそれぞれ配列番号2の配列及び配列番号3の配列をさらに有し、前記配列番号2の配列及び前記配列番号3の配列が前記配列番号1の配列の上流及び下流にそれぞれ連結して位置する、請求項13に記載の組成物。
- 前記細胞が、黒色腫、白血病、舌癌、大腸癌、食道癌、胃癌、肺がん、多発性骨髄腫、膀胱がん、乳がん、膵がん、腎がん、肝細胞癌、卵巣がん、前立腺がん、及び頭頸部扁平上皮癌からなる群より選択される腫瘍に由来する、請求項13に記載の組成物。
- 前記オリゴヌクレオチドアプタマーが、2'-アミノピリミジニル基、2'-O-メチルプリニル基、5'-ジアルキル基、ホスホロチオエートキャップ、2'-OHヌクレオチド、2'-フルオロピリミジン、又は5-(1-ペンチニル)-2'-デオキシウリジンのうち1種以上の化学基で修飾されている、請求項13に記載の組成物。
- 前記オリゴヌクレオチドアプタマーがホスホロチオエートキャップで修飾されている、請求項18に記載の組成物。
- 前記オリゴヌクレオチドアプタマーが蛍光色素、レポーター分子、造影剤、抗がん剤、ペプチド、又は粒子のいずれかに結合している、請求項13に記載の組成物。
- 前記粒子が酸化鉄磁性粒子である、請求項20に記載の組成物。
- 前記粒子が蛍光色素に結合している、請求項20に記載の組成物。
- MHCにより細胞表面にペプチドが提示された細胞を標的とする方法であって、請求項1に記載のオリゴヌクレオチドアプタマーの十分量とともに前記細胞をインキュベートすることによって前記オリゴヌクレオチドアプタマーを前記細胞に結合させることを含む方法。
- 前記ペプチドがMAGE-A3に由来する、請求項23に記載の方法。
- 前記ペプチドが配列番号4のアミノ酸配列を有する、請求項24に記載の方法。
- 前記オリゴヌクレオチドアプタマーが、配列番号2の配列及び配列番号3の配列をさらに有し、前記配列番号2の配列及び前記配列番号3の配列が前記配列番号1の配列の上流及び下流にそれぞれ連結して位置する、請求項23に記載の方法。
- 前記細胞が、黒色腫、白血病、舌癌、大腸癌、食道癌、胃癌、肺がん、多発性骨髄腫、膀胱がん、乳がん、膵がん、腎がん、肝細胞癌、卵巣がん、前立腺がん、及び頭頸部扁平上皮癌からなる群より選択される腫瘍に由来する、請求項23に記載の方法。
- 前記オリゴヌクレオチドアプタマーの安定性を増大させるために、前記オリゴヌクレオチドアプタマーが、2'-アミノピリミジニル基、2'-O-メチルプリニル基、5'-ジアルキル基、ホスホロチオエートキャップ、2'-OHヌクレオチド、2'-フルオロピリミジン、又は5-(1-ペンチニル)-2'-デオキシウリジンのうち1種以上の化学基で修飾されている、請求項23に記載の方法。
- 前記オリゴヌクレオチドアプタマーがホスホロチオエートキャップで修飾されている、請求項28に記載の方法。
- 前記オリゴヌクレオチドアプタマーが蛍光色素、レポーター分子、造影剤、抗がん剤、ペプチド、又は粒子に結合している、請求項23に記載の方法。
- 前記粒子が酸化鉄磁性粒子である、請求項30に記載の方法。
- 前記オリゴヌクレオチドアプタマーが蛍光色素に結合している、請求項30に記載の方法。
- 腫瘍の罹患が疑われる対象を治療する方法であって、前記腫瘍の進行を緩和又は寛解するために請求項1に記載のオリゴヌクレオチドアプタマーの治療的有効量を前記対象に投与することを含む方法。
- 前記オリゴヌクレオチドアプタマーが、配列番号2の配列及び配列番号3の配列をさらに有し、前記配列番号2の配列及び前記配列番号3の配列が前記配列番号1の配列の上流及び下流にそれぞれ連結して位置する、請求項33に記載の方法。
- 前記腫瘍が配列番号4のペプチドを発現している、請求項33に記載の方法。
- 前記腫瘍が、黒色腫、白血病、舌癌、大腸癌、食道癌、胃癌、肺がん、多発性骨髄腫、膀胱がん、乳がん、膵がん、腎がん、肝細胞癌、卵巣がん、前立腺がん、及び頭頸部扁平上皮癌からなる群より選択される、請求項35に記載の方法。
- 前記オリゴヌクレオチドアプタマーに結合した前記抗腫瘍剤が、メクロレタミン、シクロホスファミド、メルファラン、クロラムブチル、イホスファミド、ブスルファン、N-ニトロソ-N-メチル尿素、カルムスチン、ロムスチン、セムスチン、ホテムスチン、ストレプトゾトシン、ダカルバジン、ミトゾロミド、テモゾロミド、チオテパ、マイトマイシン、ジアジクオン、シスプラチン、カルボプラチン、オキサリプラチン、メトトレキサート、ペメトレキセド、フルオロウラシル、カペシタビン、シタラビン、ゲムシタビン、デシタビン、ビダーザ、フルダラビン、ネララビン、クラドリビン、クロファラビン、ペントスタチン、チオグアニン、メルカプトプリン、ビンカアルカロイド、タキサン、イリノテカン、トポテカン、エトポシド、ドキソルビシン、ミトキサントロン、テニポシド、ノボビオシン、メルバロン、アクラルビシン、アントラサイクリン、アクチノマイシン、ブレオマイシン、プリカマイシン、又はマイトマイシンのいずれかである、請求項33に記載の方法。
- 前記オリゴヌクレオチドアプタマーの安定性を増大させるために、前記オリゴヌクレオチドアプタマーが、2'-アミノピリミジニル基、2'-O-メチルプリニル基、5'-ジアルキル基、ホスホロチオエートキャップ、2'-OHヌクレオチド、2'-フルオロピリミジン、又は5-(1-ペンチニル)-2'-デオキシウリジンのうち1種以上の化学基で修飾されている、請求項33に記載の方法。
- 前記オリゴヌクレオチドアプタマーがホスホロチオエートキャップで修飾されている、請求項38に記載の方法。
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