JP2021509674A - 治療を強化するための細胞会合免疫アジュバント - Google Patents
治療を強化するための細胞会合免疫アジュバント Download PDFInfo
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Abstract
Description
好ましくは、細胞からの抗原放出を誘導するための手段は、ポリマーナノ粒子に封入され得る。
好ましくは、免疫アジュバント処方物は、細胞質パターン認識受容体に対するアゴニストまたはインターフェロン遺伝子刺激因子(STING)を含み得る。
好ましくは、免疫アジュバント処方物は、細胞表面上の部分を認識してそれに結合するために、小分子、ペプチド、抗体、アプタマー、糖部分、ポリマーまたはそれらの組み合わせにコンジュゲートされたアジュバントを含み得る。
好ましくは、分子は親油性または両親媒性であり得る。
好ましくは、両親媒性の分子は脂質−PEGコンジュゲートを含み得る。
好ましくは、細胞透過性ペプチドは、HIV−1 TATペプチド(GRKKRRQRRRPPQ)、ペネトラチン(RQIKIWFQNRRMKWKK)、ポリアルギニン(Rn)、またはトランスポータン(GWTLNSAGYLLGINLKALAALAKKIL)を含み得る。
好ましくは、化学薬剤は細胞毒性剤を含み得る。
好ましくは、抗原放出を誘導するための手段は、免疫アジュバント処方物の投与と同時に、必要とする対象に投与され得る。
好ましくは、方法は、細胞表面上の部分を認識してそれに結合するために、アジュバントを、小分子、ペプチド、抗体、アプタマー、糖部分、ポリマーまたはそれらの組み合わせとコンジュゲートして免疫アジュバント処方物を形成することを、さらに含み得る。
好ましくは、方法は、細胞内送達のためにナノ粒子または細胞透過性ペプチドとともにアジュバントを処方化することを、さらに含み得る。
本明細書に記載されるポリマーナノ粒子は、25nm以下の厚さを有する欠陥のない(defect−free)ポリマーシェルを有するポリマー中空ナノ粒子プラットフォームであり得る。中空ポリマーナノ粒子は、典型的には30〜600nmの外径を有する。
一般に、薄いシェルの中空ナノ粒子は、末端に高い極性のコントラストを有する両親媒性ポリマーを用いる二重エマルションプロセスに基づいて調製される。より具体的には、ジクロロメタン(DCM)中のカルボキシル末端PLGAの溶液を最初に使用して、音波分散下でカーゴを含有する水相を乳化して、エマルションを形成する。このようにして形成されたエマルションは、その後、流体分散液を使用して外水相に乳化される。
薄いシェルのポリマーナノ粒子を、以下の工程を含むプロトコルに従って製造した:
1.DCM中で10mg/mLのカルボキシ末端PLGAポリマーを調製する。
3.第1のエマルションを5mLの水溶液中で乳化し、マイクロフルイダイザーを用いて制御された流体剪断下で混合物を分散させて第2のエマルションを形成する。
5.DCMをヒュームフード中で3時間蒸発させて溶液を得る。
7.所望の溶液中に粒子を再分散させる。
ポリマーナノ粒子のキャラクタリゼーションおよび封入
上記の工程を用いて、平均直径110.9nmの中空ポリマーナノ粒子を調製した。粒子のシェル厚の統計的平均は、ナノ粒子追跡分析によって得られたパラメータに基づいて導出された。総ポリマー重量、PLGA密度、および得られたナノ粒子の数に基づいて、ナノ粒子はシェル厚さにおいて統計的平均16.5nmを有すると計算された。予想外に、ある種のポリマーナノ粒子は、40nm未満の直径を有していた。
アッセイを行い、2つの親水性高分子、すなわち核酸(色素標識20−mer一本鎖DNA)とタンパク質(色素標識BSA)に対する高分子ナノ粒子の封入効率を評価した。
リンパ節における免疫刺激に対するSTINGアゴニストの封入化および放出制御におけるポリマーナノ粒子の効果を評価するためにアッセイを行った。
全身性サイトカインを最小にしながらリンパ性サイトカインを増強するSTINGアゴニスト負荷ナノ粒子の評価
全身性サイトカインを最小にしながらリンパ性サイトカインを増強するSTINGアゴニスト負荷ナノ粒子を評価するためのアッセイを実施した。
細胞と会合する免疫アジュバント(cell−associating immunologic adjuvant)に基づく治療法
一実施形態において、本明細書に記載される治療キットおよび方法は、疾患、例えば、心血管疾患、がん、自己免疫疾患、または感染症を治療するために使用され得る。一実施形態において、本明細書に記載の治療キットおよび方法は、口腔および咽頭のがん(口唇、舌、唾液腺、口腔底、歯肉および他の口腔、鼻咽頭、扁桃、中咽頭、下咽頭、他の口腔/咽頭);消化器系のがん(食道;胃;小腸;結腸および直腸;肛門、肛門管、肛門直腸;肝臓;肝内胆管;胆嚢;他の胆道;膵臓;後腹膜腔;腹膜、大網、腸間膜;他の消化器);呼吸器系のがん(鼻腔、中耳、および副鼻腔;喉頭;肺および気管支;胸膜;気管、縦隔、およびその他の呼吸器);中皮腫;骨および関節;ならびに心臓を含む軟組織のがん;黒色腫および他の非上皮性皮膚がんを含む皮膚がん;カポジ肉腫および乳がん;女性生殖器系のがん(子宮頚部;子宮体部;子宮、卵巣;膣;外陰部;他の女性生殖器);男性生殖器系のがん(前立腺;睾丸;陰茎;他の男性生殖器);泌尿器系のがん(膀胱;腎臓および腎骨盤;尿管;その他の泌尿器);眼および眼窩のがん;脳および神経系のがん(脳;その他の神経系);内分泌系のがん(甲状腺および胸腺を含む他の内分泌);リンパ腫(ホジキン病および非ホジキンリンパ腫)、多発性骨髄腫、ならびに白血病(リンパ球性白血病;骨髄性白血病;単球性白血病;その他の白血病)、のようながんに対して使用されてもよい。
好ましい実施形態では、化学薬剤は、当技術分野で知られている任意の細胞毒性剤を含む。例えば、細胞毒性剤は、モノメチルアウリスタチンE(MMAE)、モノメチルアウリスタチンF(MMAF)、メルタンシン(DM1)、アントラサイクリン、ピロロベンゾジアゼピン、α−アマニチン、ツブリジン、ベンゾジアゼピン、エルロチニブ、ボルテゾミブ、フルベストラント、スニチニブ、レトロゾール、メシル酸イマチニブ、PTK787/ZK222584、オキサリプラチン、ロイコボリン、ラパマイシン、ラパチニブ、ロナファルニブ(SARASAE(登録商標)、SCH66336)、ソラフェニブ、ゲフィチニブ、AG1478、AG1571、アルキル化剤;アルキルスルホン酸塩;アジリジン;エチレンイミン;メチルアメラミン;アセトゲニン;カンプトテシン;ブリオスタチン;カリスタチン;CC−1065;クリプトフィシン;ドラスタチン;デュオカルマイシン;エレウテロビン;パンクラチスタチン;サルコジクチン;スポンジスタチン;クロラムブシル;クロルナファジン;クロロフォスファミド(cholosphamide);エストラムスチン;イホスファミド;メクロレタミン;メクロレタミンオキサイド塩酸塩;メルファラン;ノベンビチン;フェネステリン;プレドニムスチン;トロフォスファミド;ウラシルマスタード;カルムスチン;クロロゾトシン;ホテムスチン;ロムスチン;ニムスチン;ラニムスチン;カリケアミシン;ダイネマイシン;クロドロネート;エスペラマイシン;ネオカルジノスタチン発色団;アクラシノマイシン;アクチノマイシン;オートラマイシン;アザセリン;ブレオマイシン;カクチノマイシン;カラビシン;カミノマイシン;カルジノフィリン;クロモマイシン;ダクチノマイシン;ダウノルビシン;デトルビシン;6−ジアゾ−5−オキソ−L−ノルロイシン;ドキソルビシン;エピルビシン;エソルビシン;イダルビシン;マルセロマイシン;マイトマイシン;ミコフェノール酸;ノガラマイシン;オリボマイシン;ペプロマイシン;ポピロマイシン;ピューロマイシン;クエラマイシン;ロドルビシン;ストレプトニグリン;ストレプトゾシン、ツベルシジン、ウベニメクス、ジノスタチン、ゾルビシン;メトトレキサート;5−フルオロウラシル(5−FU);デノプテリン;プテロプテリン;トリメトレキセート;フルダラビン;6−メルカプトプリン;チアミプリン;チオグアニン;アンシタビン;アザシチジン;6−アザウリジン;カーモーファー;シタラビン;ジデオキシウリジン;ドキシフルリジン;エノシタビン;フロクスウリジン;カルステロン;プロピオン酸ドロモスタノロン;エピチオスタノール;メピチオスタン;テストラクトン;アミノグルテチミド;ミトタン;トリロスタン;フロリン酸;アセグラトン;アルドホスファミド配糖体;アミノレブリン酸;エニルウラシル;アンサクリン;ベストラブシル;ビサントレン;エダトラクセート;デホファミン;デメコルシン;ジアジコン;エルホルミジン;酢酸エリプチニウム;エポチロン;エトグルシッド;硝酸ガリウム;ヒドロキシ尿素;レンチナン;ロニダイニン;メイタンシン;アンサミトシン;ミトグアゾン;ミトキサントロン;モピダンモール;ニトラエリン;ペントスタチン;フェナメット;ピラルビシン;ロソキサントロン;ポドフィリン酸;2−エチルヒドラジド;プロカルバジン;ラゾキサン;リゾキシン;シゾフィラン;スピロゲルマニウム;テヌアゾン酸;トリアジコン;2,2’,2’’−トリクロロトリエチルアミン;トリコテセン;ウレタン;ビンデシン;ダカルバジン;マンノムスチン;ミトブロニトール;ミトラクトール;ピポブロマン;ガシトシン;アラビノシド;シクロホスファミド;チオテパ;タキソイド;パクリタキセル;ドセタキセル;クロランブシル;ゲムシタビン;6−チオグアニン;メルカプトプリン;メトトレキサート;シスプラチン;カルボプラチン;ビンブラスチン;プラチナ;エトポシド;イホスファミド;ミトキサントロン;ビンクリスチン;ビノレルビン;ノバントロン;テニポシド;エデトレキセート;ダウノマイシン;アミノプテリン;ゼロダ;イバンドロン酸;トポイソメラーゼ阻害剤;ジフルオロメチルオルニチン(DMFO);レチノイド;カペシタビン;またはその組み合わせ、を含む。
以下に列挙され、本明細書で参照される参考文献は、本明細書が別段の定めがない限り、参照により本明細書に組み込まれる。
Claims (42)
- 治療キットであって、
細胞と物理的に会合することができる免疫アジュバント処方物と、
細胞からの抗原放出を誘導するための手段と、
を含む、治療キット。 - 前記免疫アジュバント処方物は、
アジュバントを封入するポリマーナノ粒子を含み、前記ポリマーナノ粒子は、
水不透過性のポリマーシェルと、
同ポリマーシェルによって封入された1つ以上の水性コアと
を含む、請求項1に記載の治療キット。 - 前記ポリマーシェルは、25nm未満の厚さを有し、前記ポリマーナノ粒子は、30〜600nmの外径を有する、請求項2に記載の治療キット。
- 前記細胞からの抗原放出を誘導するための手段は、ポリマーナノ粒子に封入される、請求項2に記載の治療キット。
- 前記免疫アジュバント処方物は、MPLA、CpG、ポリ(I:C)、または環状ジヌクレオチドの変異体を含む、請求項1に記載の治療キット。
- 前記免疫アジュバント処方物は、細胞質パターン認識受容体に対するアゴニストまたはインターフェロン遺伝子刺激因子(STING)を含む、請求項1に記載の治療キット。
- 前記アゴニストは、環状di−GMPまたは環状GAMPである、請求項6に記載の治療キット。
- 前記免疫アジュバント処方物は、細胞表面上の部分を認識してそれに結合するために、小分子、ペプチド、抗体、アプタマー、糖部分、ポリマーまたはそれらの組み合わせにコンジュゲートされたアジュバントを含む、請求項1に記載の治療キット。
- 前記抗体は、免疫グロブリン分子、Fv、ジスルフィド結合Fv、モノクローナル抗体、scFv、キメラ抗体、単一ドメイン抗体、CDR移植抗体、ダイボディ、ヒト化抗体、多特異的抗体、Fab、二重特異的抗体、Fab’フラグメント、二重特異的抗体、F(ab’)2フラグメント、ヒンジ領域においてジスルフィド架橋によって連結された2つのFabフラグメントを含む二価フラグメント、VHドメインとCH1ドメインとからなるFdフラグメント;抗体の単一アームのVLおよびVHドメインからなるFvフラグメント、dAbフラグメント、単離された相補性決定領域(CDR)、または単鎖抗体、である、請求項8に記載の治療キット。
- 前記免疫アジュバント処方物は、細胞膜に繋留することができる分子にコンジュゲートされている、請求項1に記載の治療キット。
- 前記分子が親油性または両親媒性である、請求項10に記載の治療キット。
- 親油性分子は、脂肪酸鎖、コレステロール、またはリン脂質を含む、請求項11に記載の治療キット。
- 両親媒性分子が脂質−PEGコンジュゲートを含む、請求項11に記載の治療キット。
- 前記免疫アジュバント処方物は、細胞内送達のためにナノ粒子または細胞透過性ペプチドとコンジュゲートされたアジュバントを含む、請求項1に記載の治療キット。
- 細胞透過性ペプチドは、HIV−1 TATペプチド(GRKKRRQRRRPPQ)、ペネトラチン(RQIKIWFQNRRMKWKK)、ポリアルギニン(Rn)、またはトランスポータン(GWTLNSAGYLLGINLKALAALAKKIL)を含む、請求項14に記載の治療キット。
- 前記抗原放出を誘導するための手段は、化学薬剤、生物薬剤、放射線照射、光分解剤、機械的破壊、またはそれらの組み合わせを含む、請求項1に記載の治療キット。
- 化学薬剤が細胞毒性剤を含む、請求項16に記載の治療キット。
- 前記細胞毒性剤は、モノメチルアウリスタチンE(MMAE)、モノメチルアウリスタチンF(MMAF)、メルタンシン(DM1)、アントラサイクリン、ピロロベンゾジアゼピン、α−アマニチン、ツブリジン、ベンゾジアゼピン、エルロチニブ、ボルテゾミブ、フルベストラント、スニチニブ、レトロゾール、メシル酸イマチニブ、PTK787/ZK222584、オキサリプラチン、ロイコボリン、ラパマイシン、ラパチニブ、ロナファルニブ(SARASAE(登録商標)、SCH66336)、ソラフェニブ、ゲフィチニブ、AG1478、AG1571、アルキル化剤;アルキルスルホン酸塩;アジリジン;エチレンイミン;メチルアメラミン;アセトゲニン;カンプトテシン;ブリオスタチン;カリスタチン;CC−1065;クリプトフィシン;ドラスタチン;デュオカルマイシン;エレウテロビン;パンクラチスタチン;サルコジクチン;スポンジスタチン;クロラムブシル;クロルナファジン;クロロフォスファミド;エストラムスチン;イホスファミド;メクロレタミン;メクロレタミンオキサイド塩酸塩;メルファラン;ノベンビチン;フェネステリン;プレドニムスチン;トロフォスファミド;ウラシルマスタード;カルムスチン;クロロゾトシン;ホテムスチン;ロムスチン;ニムスチン;ラニムスチン;カリケアミシン;ダイネマイシン;クロドロネート;エスペラマイシン;ネオカルジノスタチン発色団;アクラシノマイシン;アクチノマイシン;オートラマイシン;アザセリン;ブレオマイシン;カクチノマイシン;カラビシン;カミノマイシン;カルジノフィリン;クロモマイシン;ダクチノマイシン;ダウノルビシン;デトルビシン;6−ジアゾ−5−オキソ−L−ノルロイシン;ドキソルビシン;エピルビシン;エソルビシン;イダルビシン;マルセロマイシン;マイトマイシン;ミコフェノール酸;ノガラマイシン;オリボマイシン;ペプロマイシン;ポピロマイシン;ピューロマイシン;クエラマイシン;ロドルビシン;ストレプトニグリン;ストレプトゾシン、ツベルシジン、ウベニメクス、ジノスタチン、ゾルビシン;メトトレキサート;5−フルオロウラシル(5−FU);デノプテリン;プテロプテリン;トリメトレキセート;フルダラビン;6−メルカプトプリン;チアミプリン;チオグアニン;アンシタビン;アザシチジン;6−アザウリジン;カーモーファー;シタラビン;ジデオキシウリジン;ドキシフルリジン;エノシタビン;フロクスウリジン;カルステロン;プロピオン酸ドロモスタノロン;エピチオスタノール;メピチオスタン;テストラクトン;アミノグルテチミド;ミトタン;トリロスタン;フロリン酸;アセグラトン;アルドホスファミド配糖体;アミノレブリン酸;エニルウラシル;アンサクリン;ベストラブシル;ビサントレン;エダトラクセート;デホファミン;デメコルシン;ジアジコン;エルホルミジン;酢酸エリプチニウム;エポチロン;エトグルシッド;硝酸ガリウム;ヒドロキシ尿素;レンチナン;ロニダイニン;メイタンシン;アンサミトシン;ミトグアゾン;ミトキサントロン;モピダンモール;ニトラエリン;ペントスタチン;フェナメット;ピラルビシン;ロソキサントロン;ポドフィリン酸;2−エチルヒドラジド;プロカルバジン;ラゾキサン;リゾキシン;シゾフィラン;スピロゲルマニウム;テヌアゾン酸;トリアジコン;2,2’,2’’−トリクロロトリエチルアミン;トリコテセン;ウレタン;ビンデシン;ダカルバジン;マンノムスチン;ミトブロニトール;ミトラクトール;ピポブロマン;ガシトシン;アラビノシド;シクロホスファミド;チオテパ;タキソイド;パクリタキセル;ドセタキセル;クロランブシル;ゲムシタビン;6−チオグアニン;メルカプトプリン;メトトレキサート;シスプラチン;カルボプラチン;ビンブラスチン;プラチナ;エトポシド;イホスファミド;ミトキサントロン;ビンクリスチン;ビノレルビン;ノバントロン;テニポシド;エデトレキセート;ダウノマイシン;アミノプテリン;ゼロダ;イバンドロン酸;トポイソメラーゼ阻害剤;ジフルオロメチルオルニチン(DMFO);レチノイド;カペシタビン;またはその組み合わせ、を含む、請求項17に記載の治療キット。
- 前記光分解剤は、フォトフリン、レーザーフィリン、アミノレブリン酸(ALA)、シリコンフタロシアニンPc 4、m−テトラヒドロキシフェニルクロリン(mTHPC)、クロリンe6(Ce6)、アルメラ、レブラン、フォスキャン、メトビクス、ヘクスビックス、フォトクロル、フォトセンス、フォトレックス、ルマカン、ビソナック、アンフィネックス、ベルテポルフィン、プリチン、ATMPn、亜鉛フタロシアニン(ZnPc)、プロトポルフィリンIX(PpIX)、ピロフェオホルビデア(PPa)、フェオホルビド a(PhA)、またはこれらの組み合わせ、を含む、請求項16に記載の治療キット。
- 前記免疫アジュバント処方物および前記細胞からの抗原放出を誘導するための手段が単回用量で処方化される、請求項1に記載の治療キット。
- 疾患を治療する方法であって、同方法は、
それを必要とする対象に、細胞と物理的に会合することができる免疫アジュバント処方物を投与することと、
それを必要とする対象に細胞からの抗原放出を誘導するための手段を投与することと、
を含む、方法。 - アジュバントをポリマーナノ粒子に封入することをさらに含み、前記ポリマーナノ粒子が、
水不透過性のポリマーシェルと、
ポリマーシェルによって囲まれた1つ以上の水性コアと
を含む、請求項21に記載の方法。 - 抗原放出を誘導するための手段は、免疫アジュバント処方物の投与前または投与後に、必要とする対象に投与される、請求項21に記載の方法。
- 抗原放出を誘導するための手段は、免疫アジュバント処方物と同時に、必要とする対象に投与される、請求項21に記載の方法。
- 免疫アジュバント処方物に細胞からの抗原放出を誘導するための手段を封入することをさらに含む、請求項24に記載の方法。
- 前記免疫アジュバント処方物は、MPLA、CpG、ポリ(I:C)、または環状ジヌクレオチドの変異体を含む、請求項21に記載の方法。
- 前記アジュバントは、細胞質パターン認識受容体に対するアゴニストまたはインターフェロン遺伝子刺激因子(STING)を含む、請求項21に記載の方法。
- 前記アゴニストは、環状di−GMPまたは環状GAMPである、請求項21に記載の方法。
- 細胞表面上の部分を認識してそれに結合するために、アジュバントを、小分子、ペプチド、抗体、アプタマー、糖部分、ポリマーまたはそれらの組み合わせとコンジュゲートして免疫アジュバント処方物を形成することを、さらに含む、請求項21に記載の方法。
- 前記抗体は、免疫グロブリン分子、Fv、ジスルフィド結合Fv、モノクローナル抗体、scFv、キメラ抗体、単一ドメイン抗体、CDR移植抗体、ダイボディ、ヒト化抗体、多特異的抗体、Fab、二重特異的抗体、Fab’フラグメント、二重特異的抗体、F(ab’)2フラグメント、ヒンジ領域においてジスルフィド架橋によって連結された2つのFabフラグメントを含む二価フラグメント、VHドメインとCH1ドメインとからなるFdフラグメント;抗体の単一アームのVLおよびVHドメインからなるFvフラグメント、dAbフラグメント、単離された相補性決定領域(CDR)、または単鎖抗体、である、請求項29に記載の方法。
- 細胞膜に繋留することができる分子とアジュバントとをコンジュゲートすることを、さらに含む、請求項21に記載の方法。
- 前記分子が親油性または両親媒性である、請求項31に記載の方法。
- 親油性分子は、脂肪酸鎖、コレステロール、またはリン脂質を含む、請求項32に記載の方法。
- 両親媒性分子が脂質−PEGコンジュゲートを含む、請求項32に記載の方法。
- 細胞内送達のためにナノ粒子または細胞透過性ペプチドとともにアジュバントを処方化することを、さらに含む、請求項21に記載の方法。
- 細胞透過性ペプチドは、HIV−1 TATペプチド(GRKKRRQRRRPPQ)、ペネトラチン(RQIKIWFQNRRMKWKK)、ポリアルギニン(Rn)、またはトランスポータン(GWTLNSAGYLLGINLKALAALAKKIL)を含む、請求項35に記載の方法。
- 前記抗原放出を誘導するための手段は、化学薬剤、生物薬剤、放射線照射、光分解剤、機械的破壊、またはそれらの組み合わせを含む、請求項21に記載の方法。
- 化学薬剤が細胞毒性剤を含む、請求項37に記載の方法。
- 前記細胞毒性剤は、モノメチルアウリスタチンE(MMAE)、モノメチルアウリスタチンF(MMAF)、メルタンシン(DM1)、アントラサイクリン、ピロロベンゾジアゼピン、α−アマニチン、ツブリジン、ベンゾジアゼピン、エルロチニブ、ボルテゾミブ、フルベストラント、スニチニブ、レトロゾール、メシル酸イマチニブ、PTK787/ZK222584、オキサリプラチン、ロイコボリン、ラパマイシン、ラパチニブ、ロナファルニブ(SARASAE(登録商標)、SCH66336)、ソラフェニブ、ゲフィチニブ、AG1478、AG1571、アルキル化剤;アルキルスルホン酸塩;アジリジン;エチレンイミン;メチルアメラミン;アセトゲニン;カンプトテシン;ブリオスタチン;カリスタチン;CC−1065;クリプトフィシン;ドラスタチン;デュオカルマイシン;エレウテロビン;パンクラチスタチン;サルコジクチン;スポンジスタチン;クロラムブシル;クロルナファジン;クロロフォスファミド;エストラムスチン;イホスファミド;メクロレタミン;メクロレタミンオキサイド塩酸塩;メルファラン;ノベンビチン;フェネステリン;プレドニムスチン;トロフォスファミド;ウラシルマスタード;カルムスチン;クロロゾトシン;ホテムスチン;ロムスチン;ニムスチン;ラニムスチン;カリケアミシン;ダイネマイシン;クロドロネート;エスペラマイシン;ネオカルジノスタチン発色団;アクラシノマイシン;アクチノマイシン;オートラマイシン;アザセリン;ブレオマイシン;カクチノマイシン;カラビシン;カミノマイシン;カルジノフィリン;クロモマイシン;ダクチノマイシン;ダウノルビシン;デトルビシン;6−ジアゾ−5−オキソ−L−ノルロイシン;ドキソルビシン;エピルビシン;エソルビシン;イダルビシン;マルセロマイシン;マイトマイシン;ミコフェノール酸;ノガラマイシン;オリボマイシン;ペプロマイシン;ポピロマイシン;ピューロマイシン;クエラマイシン;ロドルビシン;ストレプトニグリン;ストレプトゾシン、ツベルシジン、ウベニメクス、ジノスタチン、ゾルビシン;メトトレキサート;5−フルオロウラシル(5−FU);デノプテリン;プテロプテリン;トリメトレキセート;フルダラビン;6−メルカプトプリン;チアミプリン;チオグアニン;アンシタビン;アザシチジン;6−アザウリジン;カーモーファー;シタラビン;ジデオキシウリジン;ドキシフルリジン;エノシタビン;フロクスウリジン;カルステロン;プロピオン酸ドロモスタノロン;エピチオスタノール;メピチオスタン;テストラクトン;アミノグルテチミド;ミトタン;トリロスタン;フロリン酸;アセグラトン;アルドホスファミド配糖体;アミノレブリン酸;エニルウラシル;アンサクリン;ベストラブシル;ビサントレン;エダトラクセート;デホファミン;デメコルシン;ジアジコン;エルホルミジン;酢酸エリプチニウム;エポチロン;エトグルシッド;硝酸ガリウム;ヒドロキシ尿素;レンチナン;ロニダイニン;メイタンシン;アンサミトシン;ミトグアゾン;ミトキサントロン;モピダンモール;ニトラエリン;ペントスタチン;フェナメット;ピラルビシン;ロソキサントロン;ポドフィリン酸;2−エチルヒドラジド;プロカルバジン;ラゾキサン;リゾキシン;シゾフィラン;スピロゲルマニウム;テヌアゾン酸;トリアジコン;2,2’,2’’−トリクロロトリエチルアミン;トリコテセン;ウレタン;ビンデシン;ダカルバジン;マンノムスチン;ミトブロニトール;ミトラクトール;ピポブロマン;ガシトシン;アラビノシド;シクロホスファミド;チオテパ;タキソイド;パクリタキセル;ドセタキセル;クロランブシル;ゲムシタビン;6−チオグアニン;メルカプトプリン;メトトレキサート;シスプラチン;カルボプラチン;ビンブラスチン;プラチナ;エトポシド;イホスファミド;ミトキサントロン;ビンクリスチン;ビノレルビン;ノバントロン;テニポシド;エデトレキセート;ダウノマイシン;アミノプテリン;ゼロダ;イバンドロン酸;トポイソメラーゼ阻害剤;ジフルオロメチルオルニチン(DMFO);レチノイド;カペシタビン;またはその組み合わせ、を含む、請求項38に記載の方法。
- 前記光分解剤は、フォトフリン、レーザーフィリン、アミノレブリン酸(ALA)、シリコンフタロシアニンPc 4、m−テトラヒドロキシフェニルクロリン(mTHPC)、クロリンe6(Ce6)、アルメラ、レブラン、フォスキャン、メトビクス、ヘクスビックス、フォトクロル、フォトセンス、フォトレックス、ルマカン、ビソナック、アンフィネックス、ベルテポルフィン、プリチン、ATMPn、亜鉛フタロシアニン(ZnPc)、プロトポルフィリンIX(PpIX)、ピロフェオホルビデア(PPa)、フェオホルビド a(PhA)、またはこれらの組み合わせ、を含む、請求項37に記載の方法。
- 対象に投与することは、非経口、皮下、筋肉内、静脈内、関節内、気管支内、腹腔内、嚢内、軟骨内、腔内、皮内、小脳内、脳室内、結腸内、子宮頸管内、胃内、肝臓内、心筋内、骨内、骨盤内、心膜内、腹腔内、胸膜内、前立腺内、肺内、直腸内、腎臓内、網膜内、脊髄内、滑膜内、胸腔内、子宮内、膀胱内、ボーラス、膣、直腸、頬、舌下、経鼻、および経皮、からなる群より選択される少なくとも1つの様式によるものである、請求項21に記載の方法。
- 前記疾患が心血管疾患、癌、自己免疫疾患、または感染症である、請求項21記載の方法。
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