JP2022116265A - 両親媒性化合物、新生抗原及び疎水性担体を含むワクチン組成物、並びにその使用方法 - Google Patents
両親媒性化合物、新生抗原及び疎水性担体を含むワクチン組成物、並びにその使用方法 Download PDFInfo
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Abstract
Description
1.腫瘍特異的新生抗原を提示する癌細胞などの、その表面上に外来性の又は突然変異した抗原のエピトープを提示する体細胞において、アポトーシスを誘導できる抗原特異的細胞毒性Tリンパ球を活性化すること;
2.マクロファージ及びナチュラルキラー細胞を活性化し、細胞内病原体を破壊できるようにすること;及び
3.細胞を刺激し、適応性免疫応答及び先天性免疫応答に関与する他の細胞の機能に影響を与えるさまざまなサイトカインを分泌すること
などのさまざまな機序によって身体を保護する。
である。
である。
である。
ヒト用量(mg/kg)=動物Km
動物用量(mg/kg)=ヒトKm
(a)両親媒性化合物;
(b)新生抗原;及び
(c)疎水性担体
を含むワクチン組成物。
(a)1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)及びコレステロールの脂質分子混合物;
(b)新生抗原;
(c)疎水性担体モンタナイド(登録商標)ISA51;
(d)アミノ酸配列AQYIKANSKFIGITEL(配列番号1)を含む破傷風トキソイドからのユニバーサルヘルパーTエピトープ;及び
(e)polyI:Cポリヌクレオチドアジュバント
を含む、第1項~第27項のいずれか一項に記載の組成物。
組成物を用いた1回の免疫化のみで得られる;及び/又は
組成物中の低用量の新生抗原によって得られ、低用量が、水性ワクチン配合剤中の用量の約50%である
第20項に記載の組成物。
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Claims (41)
- (a)両親媒性化合物;
(b)新生抗原;及び
(c)疎水性担体
を含むワクチン組成物。 - 水を含まない又は水を実質的に含まない、請求項1に記載の組成物。
- 水を実質的に含まない組成物が、担体の全重量に対して、重量/重量基準で約10%、9%、8%、7%、6%、5%、4%、3%、2%、1%、0.5%、0.1%、0.05%又は0.01%未満の水を含む、請求項2に記載の組成物。
- 新生抗原が、新生抗原性ペプチド又は新生抗原性ペプチドをコードするポリヌクレオチドである、請求項1~3のいずれか一項に記載の組成物。
- 新生抗原性ペプチドが、5~50個のアミノ酸長である、請求項4に記載の組成物。
- 新生抗原性ペプチドが、1つ又は複数の新生エピトープを含む、請求項4又は5に記載の組成物。
- 1つ又は複数の新生エピトープが、9~11個のアミノ酸長のMHCクラスI T細胞新生エピトープ;13~17個のアミノ酸長のMHCクラスII T細胞新生エピトープ;又は5~20個のアミノ酸長のB細胞新生エピトープから選択される、請求項6に記載の組成物。
- 新生抗原が、アミノ酸配列PSKPSFQEFVDWENVSPELNSTDQPFL(配列番号2)を含む、請求項1~7のいずれか一項に記載の組成物。
- 新生抗原が弱免疫原性抗原である、請求項1~8のいずれか一項に記載の組成物。
- 低用量の新生抗原を含む、請求項1~9のいずれか一項に記載の組成物。
- 新生抗原が疎水性担体に混和性となるように、新生抗原が十分に疎水性である、又は十分に疎水性にされている、請求項1~10のいずれか一項に記載の組成物。
- 新生抗原が、両親媒性化合物の存在によって十分に疎水性にされており、
両親媒性化合物が、新生抗原と密接に会合し、新生抗原を疎水性担体中で混和性にしている;及び/又は
両親媒性化合物が、シート又は小胞構造を形成し、新生抗原を部分的に又は完全に囲んでいる
請求項11に記載の組成物。 - 両親媒性化合物が、リン脂質又はリン脂質の混合物から選択される脂質である、請求項1~12のいずれか一項に記載の組成物。
- 疎水性担体が、油又は油の混合物である、請求項1~13のいずれか一項に記載の組成物。
- 疎水性担体が、鉱油である、又は鉱油溶液中のオレイン酸マンニドである、請求項14に記載の組成物。
- アジュバント、ヘルパーTエピトープ、又はアジュバントとヘルパーTエピトープの両方をさらに含む、請求項1~15のいずれか一項に記載の組成物。
- アジュバントが、polyI:Cポリヌクレオチドアジュバント、脂質系アジュバント、脂質A模倣体若しくは類似体、又はこれらの任意の組合せである、請求項16に記載の組成物。
- ヘルパーTエピトープが、アミノ酸配列AKXVAAWTLKAAA(配列番号6)を含むPADRE;アミノ酸配列FNNFTVSFWLRVPKVSASHLE(配列番号7)を含む破傷風トキソイドペプチドF21E;又はアミノ酸配列AQYIKANSKFIGITEL(配列番号1)を含む修飾破傷風毒素ペプチドA16Lである、請求項16又は17に記載の組成物。
- (a)1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)及びコレステロールの脂質分子混合物;
(b)新生抗原;
(c)疎水性担体モンタナイド(登録商標)ISA51;
(d)アミノ酸配列AQYIKANSKFIGITEL(配列番号1)を含む破傷風トキソイドからのユニバーサルヘルパーTエピトープ;及び
(e)polyI:Cポリヌクレオチドアジュバント
を含む、請求項1~18のいずれか一項に記載の組成物。 - 対象において、新生抗原に対する抗体免疫応答及び/又は細胞媒介性免疫応答の誘導に使用するための、請求項1~19のいずれか一項に記載の組成物。
- 強化された細胞媒介性免疫応答をもたらし、その強化された細胞媒介性免疫応答が、新生抗原を水性ワクチン配合剤に配合したときよりも、少なくとも2倍、少なくとも3倍、少なくとも4倍、少なくとも5倍、少なくとも6倍、少なくとも7倍、少なくとも8倍、少なくとも9倍又は少なくとも10倍高い、請求項1~20のいずれか一項に記載の組成物。
- 強化された細胞媒介性免疫応答が、組成物を用いた1回の免疫化のみで得られる、請求項21に記載の組成物。
- 強化された細胞媒介性免疫応答が、組成物中の低用量の新生抗原によって得られ、低用量が、水性ワクチン配合剤中の用量の約50%である、請求項21又は22に記載の組成物。
- 新生抗原に対する抗体免疫応答及び/又は細胞媒介性免疫応答を誘導するための方法であって、請求項1~23のいずれか一項に記載の組成物を、それを必要とする対象に投与することを含む方法。
- 組成物を、対象に単回のみ投与することを含む、請求項24に記載の方法。
- 組成物が、低用量の新生抗原を含む、請求項24又は25に記載の方法。
- 癌を治療及び/又は予防するための方法である、請求項24~26のいずれか一項に記載の方法。
- DNA複製に干渉する薬剤及び/又は免疫応答チェックポイント阻害剤を対象に投与することをさらに含む、請求項24~27のいずれか一項に記載の方法。
- DNA複製に干渉する薬剤がシクロホスファミドであり、且つ免疫応答チェックポイント阻害剤が、プログラム死リガンド1(PD-L1)、プログラム死1(PD-1)、CTLA-4、PD-L2、LAG3、TIM3、41BB、2B4、A2aR、B7H1、B7H3、B7H4、BTLA、CD2、CD27、CD28、CD30、CD40、CD70、CD80、CD86、CD160、CD226、CD276、DR3、GAL9、GITR、HVEM、IDO1、IDO2、誘導性T細胞共刺激(ICOS)、KIR、LAIR1、LIGHT、コラーゲン構造を有するマクロファージ受容体(MARCO)、ホスファチジルセリン(PS)、OX-40、SLAM、TIGIT、VISTA、VTCN1、又はこれらの任意の組合せの阻害剤である、請求項28に記載の方法。
- 新生抗原に対する抗体免疫応答及び/又は細胞媒介性免疫応答を、対象において誘導するための、請求項1~23のいずれか一項に記載の組成物の使用。
- 癌を治療及び/又は予防するための、請求項1~23のいずれか一項に記載の組成物の使用。
- 組成物を、対象に単回のみ投与することを含む、請求項30又は31に記載の使用。
- 組成物が、低用量の新生抗原を含む、請求項30~32のいずれか一項に記載の使用。
- 両親媒性化合物及び新生抗原を含む第1の容器;並びに
疎水性担体を含む第2の容器
を含むキット。 - 第1の容器中の両親媒性化合物が、1,2-ジオレオイル-sn-グリセロ-3-ホスホコリン(DOPC)及びコレステロールを含む、請求項34に記載のキット。
- 第1の容器が、ヘルパーTエピトープ、アジュバント、又はヘルパーTエピトープとアジュバントの両方をさらに含む、請求項34又は35に記載のキット。
- ヘルパーTエピトープが、アミノ酸配列AQYIKANSKFIGITEL(配列番号1)を含むペプチドであり、且つアジュバントがpolyI:Cポリヌクレオチドである、請求項36に記載のキット。
- 第1の容器の構成成分が、凍結乾燥に供されて乾燥塊を形成した、請求項34~37のいずれか一項に記載のキット。
- 対象において、新生抗原に対する抗体免疫応答及び/又は細胞媒介性免疫応答の誘導に使用するための、請求項34~38のいずれか一項に記載のキット。
- 単回投与に十分な量の構成成分を含む、請求項34~39のいずれか一項に記載のキット。
- 低用量の新生抗原を含む、請求項34~40のいずれか一項に記載のキット。
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