JP2017534280A - 腫瘍を標的にするがt細胞を標的にしないサバイビン特異的t細胞受容体 - Google Patents
腫瘍を標的にするがt細胞を標的にしないサバイビン特異的t細胞受容体 Download PDFInfo
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Abstract
Description
合衆国政府の助成による研究または開発に関する陳述
I.例示的なサバイビン特異的T細胞受容体
A.タンパク質性組成物、一般
生物としては、限定されないが、以下が挙げられ、そのような悪影響又は望ましくない影響が著しい傷害性又は有害な免疫反応などのものである。好ましい実施形態では、組成物を含有する生体適合性のタンパク質、ポリペプチド、又はペプチドは一般に各々、毒素、病原体、及び有害な免疫原が本質的に存在しない哺乳類タンパク質若しくはペプチド又は合成タンパク質若しくはペプチドあることになる。
B.生物学的機能等価物
1.修飾ポリヌクレオチド及びポリペプチド
2.改変アミノ酸
3.模倣体
4.具体的な実施形態
II.サバイビン特異的TCRを発現する宿主細胞
III.医薬組成物
V.TCR及びTCRを含む宿主T細胞の治療用途
IV.本開示のキット
V.TCRをコードするポリヌクレオチド
VI.併用療法
A.化学療法
;ルビジノンB1;ルボキシル;サフィンゴール;サイントピン;SarCNU;サルコフィトールA;サルグラモスチム;Sdi1模倣剤;セムスチン;老化細胞由来阻害物質1(senescence derived inhibitor 1);センスオリゴヌクレオチド;シグナル伝達阻害剤;シゾフラン(sizofuran);ソブゾキサン;ナトリウムボロカプテイト;フェニル酢酸ナトリウム;ソルベロール(solverol);ソマトメジン結合タンパク質;ソネルミン;スパルホス酸;スピカマイシンD;スピロムスチン;スプレノペンチン;スポンギスタチン1;スクアラミン;スチピアミド;ストロメライシン阻害剤;スルフィノシン;超活性血管作動性腸管ペプチド拮抗剤;スラジスタ(suradista);スラミン;スワインソニン;タリムスチン;タモキシフェンメチオジド;タウロムスチン;タザロテン;テコガランナトリウム;テガフール;テルラピリリウム;テロメラーゼ阻害剤;テモポルフィン;テニポシド;テトラクロロデカオキシド;テトラゾミン;タリブラスチン;チオコラリン;トロンボポエチン;トロンボポエチン模倣剤;チマルファシン;チモポエチン受容体作動薬;チモトリナン;甲状腺刺激ホルモン;エチルエチオプルプリンすず;チラパザミン;二塩化チタノセン;トプセンチン;トレミフェン;翻訳阻害剤;トレチノイントリアセチルウリジン;トリシリビン;トリメトレキサート;トリプトレリン;トロピセトロン;ツロステリド;チロシンキナーゼ阻害剤;チルホスチン;UBC阻害剤;ウベニメクス;泌尿生殖洞増殖阻害因子;ウロキナーゼ受容体拮抗剤;バプレオチド;バリオリンB;ベラレゾール(velaresol);ベラミン(veramine);ベルジン;ベルテポルフィン;ビノレルビン;ビンキサルチン;ビタキシン;ボロゾール;ザノテロン;ゼニプラチン;ジラスコルブ;及びジノスタチンスチマラマー、又は前述のものいずれかのアナログ若しくは誘導体バリアント並びにまたその組み合わせが挙げられる。
B.放射線療法
C.免疫療法
D.遺伝子
E.手術
F.他の薬剤
実施例1
選択的抗腫瘍効果をもつ自己サバイビン特異的T細胞クローンの生成
実施例2
サバイビン特異的TCRを発現するように組換え操作されたポリクローナルT細胞は同胞殺しではない
実施例3
サバイビンTCRリダイレクトT細胞は正常造血前駆細胞に対する傷害性なしに抗腫瘍活性を発揮する
実施例4
サバイビンTCRトランスジェニックT細胞は生体内で抗腫瘍活性をもち、生存を向上する
実施例5
アラニンスキャニングはサバイビンエピトープの認識に最適化されたTCR結合様式を明らかにする。
実施例6
あるいくつかの実施形態のまとめ
実施例7
例示的方法
細胞株
健康な提供者及び白血病患者由来の試料
ペプチド及びアラニン置換実験
サバイビン特異的T細胞株及びクローンの生成と増殖
免疫表現型検査
ELISpotアッセイ
クロム放出アッセイ
共培養及びサイトメトリービーズアレイ
白血病及び正常造血前駆体のコロニー形成単位アッセイ(CFU)
サバイビン特異的TCR遺伝子の単離及びレトロウィルスベクターの生成
レトロウイルス上清の生成、T細胞形質導入及び増殖
BV173白血病異種移植片モデル及び生体内生物発光イメージング
交差反応性ペプチドに関するExPASy−PROSITE検索
統計的解析
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Claims (40)
- 免疫細胞を含む組成物であって、前記細胞が遺伝子操作されたサバイビン特異的T細胞受容体を含み、前記受容体が下記:
配列番号1を含む前記受容体のアルファ鎖又はその機能的断片若しくは機能的誘導体及び
配列番号2を含む前記受容体のベータ鎖又はその機能的断片若しくは機能的誘導体
の一方又は両方を含む組成物。 - 前記免疫細胞がT細胞である請求項1に記載の組成物。
- 前記細胞がT細胞受容体ではない抗原認識部分を含む請求項1に記載の組成物。
- 前記抗原認識部分が、キメラ抗原受容体、エンゲージャー分子(engager molecule)、又は他のT細胞受容体である請求項3に記載の組成物。
- 前記抗原認識部分がサバイビンを認識する請求項3に記載の組成物。
- 前記抗原認識部分がサバイビン以外の腫瘍抗原を認識する請求項3に記載の組成物。
- 前記細胞が個人にとって自己由来である請求項1に記載の組成物。
- 前記細胞が個人にとって同種異系である請求項1に記載の組成物。
- 配列番号1の前記機能的断片が配列番号1の配列のN末端トランケーションをもつ請求項1に記載の組成物。
- 前記N末端トランケーションが、配列番号1のN末端からトランケートされた1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、又は20個以上のアミノ酸である請求項9に記載の組成物。
- 配列番号1の前記機能的断片が配列番号1の配列のC末端トランケーションをもつ請求項1に記載の組成物。
- 前記C末端トランケーションが、配列番号1のC末端からトランケートされた1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、又は20個以上のアミノ酸である請求項11に記載の組成物。
- 配列番号1の前記機能的誘導体が、配列番号1に70%、75%、80%、85%、90%、95%、97%、98%、又は99%同一である請求項1に記載の組成物。
- 配列番号2の前記機能的断片が配列番号2の配列のN末端トランケーションをもつ請求項1に記載の組成物。
- 前記N末端トランケーションが、配列番号2のN末端からトランケートされた1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、又は20個以上のアミノ酸である請求項14に記載の組成物。
- 配列番号2の前記機能的断片が配列番号2の配列のC末端トランケーションをもつ請求項1に記載の組成物。
- 前記C末端トランケーションが、配列番号2のC末端からトランケートされた1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、又は20個以上のアミノ酸である請求項16に記載の組成物。
- 配列番号2の前記機能的誘導体が、配列番号2と70%、75%、80%、85%、90%、95%、97%、98%、又は99%同一である請求項1に記載の組成物。
- 配列番号1の前記機能的断片が配列番号1の配列のN末端及びC末端トランケーションをもつ請求項1に記載の組成物。
- 配列番号2の前記機能的断片が配列番号2の配列のN末端及びC末端トランケーションをもつ請求項1に記載の組成物。
- 前記細胞が自殺遺伝子産物を発現する請求項1に記載の組成物。
- 前記受容体がHLA−A2拘束性である請求項1に記載の組成物。
- 前記受容体が配列番号15を含むエピトープ又はその機能的断片若しくは誘導体、配列番号16を含むエピトープ又はその機能的断片若しくは誘導体からなる群より選択されるエピトープ、又は両者を認識する請求項1に記載の組成物。
- 配列番号15を含む前記エピトープの前記機能的断片又は誘導体が、配列番号15に70、75、77、80、85、88、90、91、91、95、97、又は99%同一である請求項23に記載の組成物。
- 配列番号16を含む前記エピトープの前記機能的断片又は誘導体が、配列番号16に70、75、77、80、85、88、90、91、91、95、97、又は99%同一である請求項23に記載の組成物。
- 前記エピトープが配列番号15に関してN末端の伸長又はトランケーションを含む請求項23に記載の組成物。
- 前記N末端及び/又はC末端の伸長が、1、2、3、4、5、6、7、8、9、又は10個以上のアミノ酸である請求項26に記載の組成物。
- 前記N末端及び/又はC末端のトランケーションが、1、2、3、4、又は5個以上のアミノ酸である請求項26に記載の組成物。
- 前記エピトープが配列番号16に関してN末端の伸長又はトランケーションを含む請求項23に記載の組成物。
- 前記N末端及び/又はC末端の伸長が、1、2、3、4、5、6、7、8、9、又は10個以上のアミノ酸である請求項29に記載の組成物。
- 前記N末端及び/又はC末端のトランケーションが、1、2、3、4、又は5個以上のアミノ酸である請求項29に記載の組成物。
- それを必要としている個人に細胞療法を提供する方法であって、治療有効量の請求項1〜31のいずれか一項に記載の前記組成物を前記個人に提供する工程を含む方法。
- 前記個人がサバイビン陽性がんをもつ請求項32に記載の方法。
- 前記サバイビン陽性がんが、白血病、骨髄腫、乳がん、肺がん、結腸がん、黒色腫、リンパ腫、卵巣がん、前立腺がん、中枢神経系がん、又は腎がんである請求項33に記載の方法。
- さらなるがん療法を前記個人に提供する工程をさらに含む請求項32に記載の方法。
- 前記さらなるがん療法が、化学療法、免疫療法、放射線、手術、又はホルモン療法である請求項35に記載の方法。
- 配列番号1、配列番号2、配列番号1及び配列番号2の組み合わせ、又は配列番号3のアミノ酸配列を発現するポリヌクレオチド。
- 前記ポリヌクレオチドが発現ベクターである請求項37に記載のポリヌクレオチド。
- 請求項37〜38のいずれか一項に記載の前記ポリヌクレオチドを含む細胞。
- 請求項1〜31のいずれか一項に記載の前記組成物、請求項37〜38のいずれか一項に記載のポリヌクレオチド、請求項39に記載の細胞、又はそれら組み合わせを含むキット。
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LT2618835T (lt) * | 2010-09-20 | 2017-10-10 | Biontech Cell & Gene Therapies Gmbh | Antigenui specifiniai t ląstelių receptoriai ir t ląstelių epitopai |
EP3533802B1 (en) * | 2010-09-21 | 2021-03-17 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Anti-ssx-2 t cell receptors and related materials and methods of use |
EP3766896A1 (en) * | 2011-09-15 | 2021-01-20 | The United States of America, as represented by The Secretary, Department of Health and Human Services | T cell receptors recognizing hla-a1- or hla-cw7-restricted mage |
GB2508414A (en) * | 2012-11-30 | 2014-06-04 | Max Delbrueck Centrum | Tumour specific T cell receptors (TCRs) |
-
2015
- 2015-10-30 CA CA2965521A patent/CA2965521A1/en not_active Abandoned
- 2015-10-30 US US15/522,698 patent/US20170335290A1/en not_active Abandoned
- 2015-10-30 WO PCT/US2015/058452 patent/WO2016070119A1/en active Application Filing
- 2015-10-30 EP EP15854854.5A patent/EP3212774A4/en not_active Withdrawn
- 2015-10-30 JP JP2017522878A patent/JP2017534280A/ja active Pending
- 2015-10-30 AU AU2015338958A patent/AU2015338958A1/en not_active Abandoned
- 2015-10-30 KR KR1020177014789A patent/KR20170076775A/ko unknown
- 2015-10-30 SG SG11201703309PA patent/SG11201703309PA/en unknown
- 2015-10-30 CN CN201580062266.1A patent/CN107002043A/zh active Pending
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AU2015338958A1 (en) | 2017-05-11 |
CA2965521A1 (en) | 2016-05-06 |
SG11201703309PA (en) | 2017-05-30 |
EP3212774A1 (en) | 2017-09-06 |
CN107002043A (zh) | 2017-08-01 |
KR20170076775A (ko) | 2017-07-04 |
US20170335290A1 (en) | 2017-11-23 |
WO2016070119A1 (en) | 2016-05-06 |
EP3212774A4 (en) | 2018-04-11 |
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