JP6788500B2 - Muc1−c癌タンパク質のhla−a24アゴニストエピトープ及び組成物及び使用方法 - Google Patents
Muc1−c癌タンパク質のhla−a24アゴニストエピトープ及び組成物及び使用方法 Download PDFInfo
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- JP6788500B2 JP6788500B2 JP2016525904A JP2016525904A JP6788500B2 JP 6788500 B2 JP6788500 B2 JP 6788500B2 JP 2016525904 A JP2016525904 A JP 2016525904A JP 2016525904 A JP2016525904 A JP 2016525904A JP 6788500 B2 JP6788500 B2 JP 6788500B2
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Description
本特許出願は、2013年10月23日出願の米国仮特許出願第61/894,482号(参照により組み込まれる)の利益を主張する。
本明細書と同時提出の、ヌクレオチド/アミノ酸の配列表は、その全体が参照により本明細書に組み込まれる。
MUC1(CD227)は、大型のN末端サブユニット(MUC1−N)が、小型のC末端サブユニット(MUC1−C)に共有結合したヘテロダイマーから構成される、I型膜糖タンパク質である。
本発明は、配列番号1又は配列番号2のアミノ酸配列を含むペプチドを提供する。
本発明は、MUC1を発現又は過剰発現する癌を含むが、それらに限定されない癌の、予防又は治療的処置のためのワクチン及び他の組成物に用いられ得る、ヒト腫瘍関連抗原(TAA)のムチン1(MUC1)及びその類似体の、C末端サブユニットからのヒト細胞傷害性Tリンパ球(CTL)エピトープを含む、ペプチドを提供する。特に、本発明は、KYHPMSEYAL(配列番号1)又はKYTNPAVAL(配列番号2)のアミノ酸配列を含む、それらから本質的になる、又はそれらからなるペプチド、ポリペプチド、及びタンパク質を提供する。
本実施例では、HLA−A24 MUC1−Cアゴニストエピトープの解析について説明する。
本実施例では、配列番号1を含み、GI−6108として知られる、酵母ベースのMUC1アゴニスト免疫療法組成物の製造を実証する。
本実施例では、GI−6108及びGI−6108−DECとして知られる本発明の酵母−MUC1免疫療法組成物が、MUC1特異的T細胞を活性化し得ることを実証する。
本実施例では、MUC1陽性の癌を患う被験体における第1相臨床試験について説明する。
本実施例では、MUC1−CのHLA−A24アゴニストエピトープが、MUC1特異的細胞を活性化し得ることを実証する。
Claims (56)
- 配列番号1のアミノ酸配列から成るMUC1ペプチドであって、アゴニストエピトープとして機能する、ペプチド。
- 請求項1のペプチドをコードする核酸。
- 請求項2の核酸を含むベクター。
- (i)請求項1のペプチドの1以上、(ii)請求項2の核酸の1以上、又は(iii)請求項3のベクターの1以上を含む、細胞。
- 細胞がヒトのである、請求項4の細胞。
- 抗原提示細胞又は腫瘍細胞である、請求項4又は5の細胞。
- (a)(i)請求項1のペプチド、(ii)請求項2の核酸、(iii)請求項3のベクター又は(iv)請求項4〜6のいずれか1項の細胞の、1以上、及び
(b)医薬的に許容可能な担体
を含む、組成物。 - 免疫刺激/調節分子を更に含む、請求項7の組成物。
- 免疫刺激/調節分子が、インターロイキン(IL)−2、IL−4、IL−6、IL−12、IL−15、IL−15/IL15Ra、IL−15/IL−15Ra−Fc、インターフェロン(IFN)−γ、腫瘍壊死因子(TNF)−α、B7.1、B7.2、ICAM−1、LFA−3、CD70、RANTES、G−CSF、OX−40L、41BBL、抗CTLA−4、IDO阻害剤、抗PDL1、抗PD1、及びこれらの組み合わせから成る群から選択される、請求項8の組成物。
- 免疫刺激/調節分子が、(i)キトサンと複合体化されたIL−12をコードするプラスミド及び(ii)キトサンと混合された組換えIL−12から成る群から選択される、請求項8の組成物。
- 化学療法薬、放射性薬剤、代謝拮抗剤、ホルモン、ホルモンアンタゴニスト、抗生物質、抗ウイルス薬、抗真菌薬、シクロホスファミド、又はそれらの組み合わせを更に含む、請求項7〜10のいずれか1項の組成物。
- アルキル化剤、葉酸アンタゴニスト、プリンアンタゴニスト、ピリミジンアンタゴニスト、紡錘体毒、トポイソメラーゼ阻害剤、アポトーシス誘導剤、血管新生阻害剤、ポドフィロトキシン、ニトロソウレア、シスプラチン、カルボプラチン、インターフェロン、アスパラギナーゼ、タモキシフェン、ロイプロリド、フルタミド、メゲストロール、マイトマイシン、ブレオマイシン、ドキソルビシン、イリノテカン、タキソール、ゲルダナマイシン、又はそれらの組み合わせを更に含む、請求項7〜10のいずれか1項の組成物。
- アドリアマイシン、アルケラン、アラC、ブスルファン、CCNU、カルボプラチン、シスプラチン、サイトキサン、ダウノルビシン、DTIC、5−FU、フルダラビン、ハイドレア、イダルビシン、イホスファミド、メトトレキサート、ミトラマイシン、マイトマイシン、ミトキサントロン、ナイトロジェンマスタード、タキソール、ベルバン、ビンクリスチン、VP−16、ゲムシタビン、ハーセプチン、イリノテカン、ロイスタチン、ナベルビン、リツキサンSTI−571、タキソテール、トポテカン、カペシタビン、ゼベリン、エンザルタミド、カルシトリオール、又はそれらの組み合わせを更に含む、請求項7〜10のいずれか1項の組成物。
- 1以上のアジュバントを更に含む、請求項7〜13のいずれか1項の組成物。
- 1以上のアジュバントが、アラム、アルミニウム塩、リン酸アルミニウム、水酸化アルミニウム、ケイ酸アルミニウム、リン酸カルシウム、不完全フロイントアジュバント、QS21、MPL−A、RIBI DETOX(商標)、及びそれらの組み合わせから成る群から選択される、請求項14の組成物。
- 顆粒球単球コロニー刺激因子(GM−CSF)を更に含む、請求項7〜15のいずれか1項の組成物。
- リポソームを更に含む、請求項7〜16のいずれか1項の組成物。
- 被験体においてMUC1を発現する癌に対する免疫応答を増強するための、請求項7〜17のいずれか1項の組成物。
- 被験体においてMUC1を発現する癌を阻害するための、請求項7〜17のいずれか1項の組成物により刺激されたリンパ球を含む、組成物。
- 被験体においてMUC1を発現する癌を阻害するための、請求項7〜17のいずれか1項の組成物により処理された樹状細胞を含む、組成物。
- 被験体においてMUC1を発現する癌を阻害するための、請求項7〜17のいずれか1項の組成物によりin vitroで刺激した養子移入T細胞を含む、組成物。
- 酵母−MUC1免疫療法組成物であって:
(a)酵母ビヒクル;及び
(b)少なくとも1のムチン1(MUC1)抗原を含む融合蛋白質であって、融合蛋白質は、配列番号16のアミノ酸配列に対して少なくとも95%同一のアミノ酸配列を含み、且つ配列番号1のアミノ酸配列から成るMUC1抗原を更に含む、
を含む、免疫療法組成物。 - 酵母−MUC1免疫療法組成物であって:
(a)酵母ビヒクル;及び
(b)少なくとも1のMUC1抗原を含む、融合タンパク質であって、融合タンパク質が、配列番号16のアミノ酸配列を含み、
MUC1抗原が、配列番号16の92位〜566位から成る、及び
MUC1抗原が、配列番号1のアミノ酸配列を含む、融合タンパク質
を含む、免疫療法組成物。 - 酵母−MUC1免疫療法組成物であって:
(a)酵母ビヒクル;及び
(b)少なくとも1のMUC1抗原を含む、融合タンパク質であって、MUC1抗原が、野生型MUC1のアミノ酸配列に関して以下:T422K、P430A、及びT431Lのアミノ酸置換によって配列番号14を有する野生型MUC1タンパク質のアミノ酸配列とは異なるアミノ酸配列を有する、融合タンパク質
を含む、免疫療法組成物。 - MUC1抗原が、野生型MUC1のアミノ酸配列に関して更に:T93、A161、P162、G169、S170、T171、A392、C406、T444、D445、及びS460の位置にアミノ酸置換を含む、請求項24の酵母−MUC1免疫療法組成物。
- MUC1抗原が、野生型MUC1のアミノ酸配列に関して、C404位のアミノ酸の置換を更に含む、請求項24又は25の酵母−MUC1免疫療法組成物。
- MUC1抗原が、野生型MUC1のアミノ酸配列に関して更に以下:T93L、A161Y、P162L、G169V、S170Y、T171L、A392Y、C404A、C406V、T444L、D445F、及びS460Yから選択されるアミノ酸置換を含む、請求項24〜26のいずれか1項の酵母−MUC1免疫療法組成物。
- 酵母ビヒクルが全酵母である、請求項22〜27のいずれか1項の酵母−MUC1免疫療法組成物。
- 融合タンパク質が酵母により発現されている、請求項22〜28のいずれか1項の酵母−MUC1免疫療法組成物。
- 酵母ビヒクルが熱で不活性化されている、請求項22〜29のいずれか1項の酵母−MUC1免疫療法組成物。
- 酵母ビヒクルがサッカロマイセス・セレビシエ由来である、請求項22〜30のいずれか1項の酵母−MUC1免疫療法組成物。
- 5.5〜8のpHレベルで維持された培地中で、MUC1抗原を発現する全酵母を培養することにより製造された、請求項22〜31のいずれか1項の酵母−MUC1免疫療法組成物。
- 個体における全身腫瘍組織量を減少させ、腫瘍の成長を阻害し、及び/又はMUC1を発現する癌を有する個体の生存を増加させるための、請求項22〜32のいずれか1項の酵母−MUC1免疫療法組成物。
- MUC1発現が、組成物が最初に投与される時に、個体の癌で検出される、請求項33の酵母−MUC1免疫療法組成物。
- 個体が、少なくとも1の、癌に対する更なる治療法で治療されているか、又は治療されていた、請求項33又は請求項34の酵母−MUC1免疫療法組成物。
- 少なくとも1の更なる治療法が、化学療法、標的癌療法、放射線療法、養子T細胞移入、及び/又は1以上の更なる免疫療法組成物の投与から選択される、請求項35の酵母−MUC1免疫療法組成物。
- 個体におけるMUC1を発現する癌の発症を予防する、又は遅延させるための、請求項22〜32のいずれか1項の酵母−MUC1免疫療法組成物。
- 個体において癌が検出されていない、請求項37の酵母−MUC1免疫療法組成物。
- 個体が癌を発症するリスクが高い、請求項38の酵母−MUC1免疫療法組成物。
- 癌が上皮細胞起源である、請求項33〜39のいずれか1項の酵母−MUC1免疫療法組成物。
- 癌が:乳癌、小腸癌、胃癌、膵臓癌、腎臓癌、膀胱癌、子宮癌、卵巣癌、精巣癌、肺癌、結腸癌、前立腺癌、黒色腫、食道癌、多発性骨髄性白血病(MML)、慢性リンパ球性白血病(CLL)、急性骨髄性白血病(AML)、バーキットリンパ腫、ホジキンリンパ腫、分泌組織の癌、及びそれらの転移性癌から成る群から選択される、請求項33〜39のいずれか1項の酵母−MUC1免疫療法組成物。
- 癌の治療に使用するための、請求項22〜32のいずれか1項の酵母−MUC1免疫療法組成物。
- 癌を有する個体において癌の転移の進行を減退させること、阻止すること、反転させること、又は予防することに用いるための、請求項22〜32のいずれか1項の酵母−MUC1免疫療法組成物。
- 癌を治療することに用いるための医薬の調製における、請求項22〜32のいずれか1項の酵母−MUC1免疫療法組成物の使用。
- 癌を有する個体において、癌の転移の進行を減退させること、阻止すること、反転させること、又は予防することに用いるための医薬の調製における、請求項22〜32のいずれか1項の酵母−MUC1免疫療法組成物の使用。
- MUC1を発現する癌の発症を予防すること又は遅延させることに用いるための医薬の調製における、請求項22〜32のいずれか1項の酵母−MUC1免疫療法組成物の使用。
- 配列番号16のアミノ酸配列に対して少なくとも95%同一のアミノ酸配列を含み、且つ配列番号1から成るアミノ酸配列を更に含む、MUC1タンパク質。
- 被験体においてMUC1を発現する癌に対する免疫応答を誘導するための、
(a)請求項1のペプチドをコードする核酸を含む第一のポックスウイルスベクター及び
(b)請求項1のペプチドをコードする核酸を含む第二のポックスウイルスベクター
を含む、組み合わせ組成物。 - 被験体においてMUC1を発現する癌に対する免疫応答を誘導するための、
(a)請求項47のMUC1タンパク質をコードする核酸を含む第一のポックスウイルスベクター及び
(b)請求項47のMUC1タンパク質をコードする核酸を含む第二のポックスウイルスベクター
を含む、組み合わせ組成物。 - 第一及び第二のポックスウイルスベクターが、癌胎児性抗原(CEA)をコードする核酸を更に含む、請求項48又は49の組み合わせ組成物。
- 第一及び第二のポックスウイルスベクターが、1以上の共刺激分子をコードする核酸を更に含む、請求項48〜50のいずれか1項の組み合わせ組成物。
- 1以上の共刺激分子が、B7.1、ICAM−1、及びLFA−3から選択される、請求項51の組み合わせ組成物。
- 第一のポックスウイルスベクターがワクシニアウイルスであり、及び第二のポックスウイルスベクターが鶏痘ウイルスである、請求項48〜52のいずれか1項の組み合わせ組成物。
- 第一のポックスウイルスベクターが、修飾ワクシニアアンカラ(MVA)ウイルスであり、及び第二のポックスウイルスベクターが鶏痘ウイルスである、請求項48〜52のいずれか1項の組み合わせ組成物。
- MVAウイルスがMVA−BNである、請求項54の組み合わせ組成物。
- 第一及び第二のポックスウイルスベクターが、プライム−ブーストプロトコルで被験体への投与に使用するための、請求項48〜55のいずれか1項の組み合わせ組成物。
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PCT/US2014/061723 WO2015061416A2 (en) | 2013-10-23 | 2014-10-22 | Hla-a24 agonist epitopes of muc1-c oncoprotein and compositions and methods of use |
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