JP2016508725A5 - - Google Patents
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- JP2016508725A5 JP2016508725A5 JP2015558946A JP2015558946A JP2016508725A5 JP 2016508725 A5 JP2016508725 A5 JP 2016508725A5 JP 2015558946 A JP2015558946 A JP 2015558946A JP 2015558946 A JP2015558946 A JP 2015558946A JP 2016508725 A5 JP2016508725 A5 JP 2016508725A5
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Claims (49)
- キメラ抗原受容体(CAR)をコードする単離核酸分子であって、該CARが抗EGFRvIII結合ドメイン、膜貫通ドメインおよび、一次シグナル伝達ドメインを含む細胞内シグナル伝達ドメインを含み、該抗EGFRvIII結合ドメインが表2または配列番号11に示す任意の抗EGFRvIII軽鎖結合ドメインアミノ酸配列の軽鎖相補決定領域1 (LC CDR1)、軽鎖相補決定領域2 (LC CDR2)および軽鎖相補決定領域3 (LC CDR3)の1つ以上、ならびに表2または配列番号11に示す任意の抗EGFRvIII重鎖結合ドメインアミノ酸配列の重鎖相補決定領域1 (HC CDR1)、重鎖相補決定領域2 (HC CDR2)および重鎖相補決定領域3 (HC CDR3)の1つ以上を含む、単離核酸分子。
- (a)表2または配列番号11に示す任意の抗EGFRvIII軽鎖結合ドメインアミノ酸配列のLC CDR1、LC CDR2およびLC CDR3;(b)表2または配列番号11に示す任意の抗EGFRvIII重鎖結合ドメインアミノ酸配列のHC CDR1、HC CDR2およびHC CDR3;または(c)表2または配列番号11に示す任意の抗EGFRvIII軽鎖結合ドメインアミノ酸配列のLC CDR1、LC CDR2およびLC CDR3ならびに表2または配列番号11に示す任意の抗EGFRvIII重鎖結合ドメインアミノ酸配列のHC CDR1、HC CDR2およびHC CDR3を含む、請求項1記載の単離核酸分子。
- (a)表2または配列番号11に示す任意の軽鎖可変領域;(b)表2または配列番号11に示す任意の重鎖可変領域;または(c)表2または配列番号11に示す任意の軽鎖可変領域および表2または配列番号11に示す任意の重鎖可変領域を含む、請求項1記載の単離核酸分子。
- EGFRvIII結合ドメインがscFvである、請求項1〜3のいずれか一項に記載の単離核酸分子。
- (a)軽鎖可変領域が、表2または配列番号11に記載の軽鎖可変領域のアミノ酸配列に少なくとも1個、2個または3個の変更を有するが、30個以下、20個以下または10個以下の変更を有するアミノ酸配列か、または表2または配列番号11に示すアミノ酸配列と95〜99%の同一性を有する配列を含む;(b)重鎖可変領域が、表2または配列番号11に記載の重鎖可変領域のアミノ酸配列に少なくとも1個、2個または3個の変更を有するが、30個以下、20個以下または10個以下の変更を有するアミノ酸配列か、または表2または配列番号11に示すアミノ酸配列と95〜99%の同一性を有する配列を含む;あるいは(c)(a)および(b)の両方である、請求項1〜4のいずれか一項に記載の単離核酸分子。
- 該抗EGFRvIII結合ドメインが、配列番号38、配列番号44、配列番号50、配列番号56、配列番号62、配列番号68、配列番号74、配列番号80および配列番号86からなる群から選択される配列または、それと95〜99%の同一性を有する配列を含む、請求項1〜5のいずれか一項に記載の単離核酸分子。
- 該抗EGFRvIII結合ドメインをコードする核酸配列が、配列番号39、配列番号45、配列番号51、配列番号57、配列番号63、配列番号69、配列番号75、配列番号81 および配列番号98からなる群から選択される配列または、それと95〜99%の同一性を有する配列を含む、請求項1〜6のいずれか一項に記載の単離核酸分子。
- コードされたCARが、T細胞受容体のα鎖、β鎖またはζ鎖、CD28、CD3ε、CD45、CD4、CD5、CD8、CD9、CD16、CD22、CD33、CD37、CD64、CD80、CD86、CD134、CD137およびCD154からなる群から選択されるタンパク質の膜貫通ドメインを含む膜貫通ドメインを含む、請求項1〜7のいずれか一項に記載の単離核酸分子。
- コードされた膜貫通ドメインが、配列番号15の配列、あるいは配列番号15のアミノ酸配列に少なくとも1個、2個または3個の変更を有するが、20個以下、10個以下または5個以下の変更を有するアミノ酸配列か、または配列番号15のアミノ酸配列と95〜99%の同一性を有する配列を含む、請求項1〜8のいずれか一項に記載の単離核酸分子。
- 膜貫通ドメインをコードする核酸配列が、配列番号8の配列またはそれと95〜99%の同一性を有する配列を含む、請求項1〜9のいずれか一項に記載の単離核酸分子。
- コードされた抗EGFRvIII結合ドメインが、ヒンジ領域によって膜貫通ドメインに結合している、請求項1〜10のいずれか一項に記載の単離核酸分子。
- コードされたヒンジ領域が、配列番号14またはそれと95〜99%の同一性を有する配列を含む、請求項11記載の単離核酸分子。
- ヒンジ領域をコードする核酸配列が、配列番号7の配列またはそれと95〜99%の同一性を有する配列を含む、請求項11記載の単離核酸分子。
- 同時刺激ドメインをコードする配列をさらに含む、請求項1〜13のいずれか一項に記載の単離核酸分子。
- コードされた同時刺激ドメインが、OX40、CD27、CD28、CDS、ICAM-1、LFA-1 (CD11a/CD18)、ICOS (CD278)および4-1BB (CD137)からなる群から選択されるタンパク質の機能性シグナル伝達ドメインを含む、請求項14記載の単離核酸分子。
- コードされた同時刺激ドメインが、配列番号16の配列、あるいは配列番号16のアミノ酸配列に少なくとも1個、2個または3個の変更を有するが、20個以下、10個以下または5個以下の変更を有するアミノ酸配列か、または配列番号16のアミノ酸配列と95〜99%の同一性を有する配列を含む、請求項14または15記載の該単離核酸分子。
- 同時刺激ドメインをコードする核酸配列が、配列番号9の配列またはそれと95〜99%の同一性を有する配列を含む、請求項14または15記載の単離核酸分子。
- コードされた細胞内シグナル伝達ドメインが4-1BBの機能性シグナル伝達ドメインおよびCD3ζの機能性シグナル伝達ドメインを含む、請求項1〜17のいずれか一項に記載の単離核酸分子。
- コードされた細胞内シグナル伝達ドメインが、配列番号16の配列および/または配列番号17または配列番号99の配列、あるいは配列番号16の配列および/または配列番号17または配列番号99のアミノ酸配列に少なくとも1個、2個または3個の変更を有するが、20個以下、10個以下または5個以下の変更を有するアミノ酸配列か、または配列番号16の配列および/または配列番号17または配列番号99のアミノ酸配列と95〜99%の同一性を有する配列を含む、請求項1〜18のいずれか一項に記載の単離核酸分子。
- 該コードされた細胞内シグナル伝達ドメインが、配列番号16の配列および、配列番号17または配列番号99の配列を含む、該細胞内シグナル伝達ドメインを含む配列が同一フレーム内で、単一のポリペプチド鎖として発現する、請求項1〜19のいずれか一項に記載の単離核酸分子。
- 該細胞内シグナル伝達ドメインをコードする核酸配列が、配列番号9の配列またはそれと95〜99%の同一性を有する配列および/または配列番号10または配列番号100の配列またはそれと95〜99%の同一性を有する配列を含む、請求項1〜20のいずれか一項に記載の単離核酸分子。
- リーダー配列をさらに含む、請求項1〜21のいずれか一項に記載の単離核酸分子。
- リーダー配列が、配列番号13を含む、請求項22記載の単離核酸分子。
- 請求項1〜23のいずれか一項に記載の核酸分子によりコードされている単離ポリペプチド分子。
- 配列番号43、配列番号49、配列番号55、配列番号61、配列番号67、配列番号73、配列番号79、配列番号85および配列番号90からなる群から選択される配列またはそれと95〜99%の同一性を有する配列を含む、請求項24記載の単離ポリペプチド分子。
- 抗EGFRvIII結合ドメイン、膜貫通ドメインおよび細胞内シグナル伝達ドメインを含む、単離キメラ抗原受容体(CAR)分子。
- 該細胞内シグナル伝達ドメインが同時刺激ドメインおよび一次シグナル伝達ドメインを含む、請求項26記載の単離CAR分子。
- 該抗EGFRvIII結合ドメインが、表2または配列番号11に示す任意の抗EGFRvIII結合ドメインの軽鎖相補決定領域1 (LC CDR1)、軽鎖相補決定領域2 (LC CDR2)および軽鎖相補決定領域3 (LC CDR3)の1つ以上ならびに、表2または配列番号11に示す任意の抗EGFRvIII結合ドメインの重鎖相補決定領域 1 (HC CDR1)、重鎖相補決定領域2 (HC CDR2)および重鎖相補決定領域3 (HC CDR3) の1つ以上を含む、請求項26または27記載の単離CAR分子。
- 該抗EGFRvIII結合ドメインがヒンジ領域によって膜貫通ドメインに結合している、請求項26〜28のいずれか一項に記載の単離CAR分子。
- リーダー配列をさらに含む、請求項26〜29のいずれか一項に記載の単離CAR分子。
- 配列番号38、44、50、56、62、68、74または80に示す抗EGFRvIII結合ドメインの軽鎖相補決定領域1 (LC CDR1)、軽鎖相補決定領域2 (LC CDR2)および軽鎖相補決定領域3 (LC CDR3)の1つ以上ならびに、配列番号38、44、50、56、62、68、74または80に示す抗EGFRvIII結合ドメインの重鎖相補決定領域1 (HC CDR1)、重鎖相補決定領域2 (HC CDR2)および重鎖相補決定領域3 (HC CDR3)の1つ以上を含む、抗EGFRvIII結合ドメイン。
- 配列番号38、配列番号44、配列番号50、配列番号56、配列番号62、配列番号68、配列番号74、配列番号80および配列番号86からなる群から選択される配列またはそれと95〜99%の同一性を有する配列を含む、請求項31記載の抗EGFRvIII結合ドメイン。
- 請求項1〜23のいずれか一項に記載の核酸分子を含む、ベクター。
- DNA、RNA、プラスミド、レンチウイルスベクター、アデノウイルスベクターおよびレトロウイルスベクターからなる群から選択される、請求項33記載のベクター。
- プロモーターをさらに含む、請求項33または34記載のベクター。
- 該プロモーターがEF-1プロモーターである、請求項35記載のベクター。
- 該EF-1プロモーターが配列番号97の配列を含む、請求項36記載のベクター。
- 該ベクターが試験管内で転写されたベクターである、請求項33〜37のいずれか記載のベクター。
- ベクター中の核酸配列がさらにポリ(A)テールを含む、請求項33〜38のいずれか記載のベクター。
- ベクター中の核酸配列がさらに3’UTRを含む、請求項33〜39のいずれか記載のベクター。
- 請求項33〜40のいずれか記載のベクターを含む細胞。
- T細胞である、請求項41記載の細胞。
- 該T細胞がCD8+ T細胞である、請求項42記載の細胞。
- ヒト細胞である、請求項41または42記載の細胞。
- 請求項33〜40のいずれか一項に記載のベクターでT細胞に形質導入することを含む、細胞の作製方法。
- 試験管内で転写されたRNAまたは合成RNAを細胞に導入することを含む、RNA操作細胞集団の作製方法であって、該RNAが請求項1〜23のいずれか一項に記載の核酸分子を含む、方法。
- 請求項41〜44のいずれか一項に記載の細胞を有効量で哺乳動物に投与することを含む、哺乳動物に抗腫瘍免疫を提供する方法。
- EGFRvIIIの発現に関連する疾患に罹患している哺乳動物の処置方法であって、該哺乳動物に、請求項41〜44のいずれか一項に記載の細胞を有効量で投与することを含む、方法。
- EGFRvIIIの発現に関連する疾患が、多形神経膠芽腫 (GBM)、未分化星状細胞腫、巨細胞神経膠芽腫、膠肉腫、未分化乏突起神経膠腫、未分化上衣腫、脈絡叢がん、未分化神経節膠腫、松果体芽腫、髄上皮腫、上衣芽腫、髄芽腫、テント上原始神経外胚葉性腫瘍、AT/RT(非定型奇形腫様/ラブドイド腫瘍)、肺がん(例えば非小細胞肺がん)、乳がん、前立腺がん、卵巣がん、結腸直腸がんおよび膀胱がんからなる群から選択されるがんまたはその任意の組合せ、または任意のがんの転移である、請求項48記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361767071P | 2013-02-20 | 2013-02-20 | |
US61/767,071 | 2013-02-20 | ||
US201361888255P | 2013-10-08 | 2013-10-08 | |
US61/888,255 | 2013-10-08 | ||
PCT/US2014/017364 WO2014130657A1 (en) | 2013-02-20 | 2014-02-20 | Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor |
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JP2019214013A Division JP7189860B2 (ja) | 2013-02-20 | 2019-11-27 | ヒト化抗EGFRvIIIキメラ抗原受容体を用いたがんの処置 |
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JP2016508725A JP2016508725A (ja) | 2016-03-24 |
JP2016508725A5 true JP2016508725A5 (ja) | 2017-03-23 |
JP6647868B2 JP6647868B2 (ja) | 2020-02-14 |
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JP2015558946A Active JP6647868B2 (ja) | 2013-02-20 | 2014-02-20 | ヒト化抗EGFRvIIIキメラ抗原受容体を用いたがんの処置 |
JP2019214013A Active JP7189860B2 (ja) | 2013-02-20 | 2019-11-27 | ヒト化抗EGFRvIIIキメラ抗原受容体を用いたがんの処置 |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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JP7340638B2 (ja) | 2016-06-27 | 2023-09-07 | ジュノー セラピューティクス インコーポレイテッド | Mhc-e拘束性エピトープ、結合分子ならびに関連する方法および使用 |
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