JP2021501587A - Cd38指向性キメラ抗原受容体構築物 - Google Patents
Cd38指向性キメラ抗原受容体構築物 Download PDFInfo
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Abstract
Description
配列表
定義
抗CD38キメラ抗原受容体(CAR)
宿主細胞
治療方法および抗CD38 CARの使用
抗CD38 A2 CARを発現するレトロウイルスベクターの構築
(実施例1)
細胞系、抗体およびCD38−Fc融合タンパク質
(実施例2)
CAR2−抗CD38 CARによるT細胞のレトロウイルス媒介性形質導入
(実施例3)
ウエスタンブロット
(実施例4)
フローサイトメトリー分析
(実施例5)
T細胞活性化アッセイ
(実施例6)
T細胞の細胞傷害性アッセイ
(実施例7)
NSGマウスにおけるMM異種移植片の処置
Claims (30)
- i)配列番号1のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む重鎖可変(VH)ドメインを含み、配列番号3のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む軽鎖可変(VL)ドメインを含む、CD38に結合する抗原結合性タンパク質;
ii)膜貫通ドメイン;および
iii)細胞内ドメイン
を含む抗CD38キメラ抗原受容体(CAR)構築物。 - 前記重鎖可変(VH)ドメインと前記軽鎖可変(VL)ドメインとの間にペプチドリンカーをさらに含み、前記ペプチドリンカーが、配列番号5のアミノ酸配列を含む、請求項1に記載の抗CD38キメラ抗原受容体(CAR)構築物。
- 前記抗原結合性タンパク質が、配列番号12のアミノ酸配列を含む、請求項1に記載の抗CD38キメラ抗原受容体(CAR)構築物。
- 前記抗原結合性タンパク質と前記膜貫通ドメインとの間にヒンジ領域をさらに含み、前記ヒンジ領域が、配列番号6のアミノ酸配列を含む、請求項1に記載の抗CD38キメラ抗原受容体(CAR)構築物。
- 前記抗原結合性タンパク質と前記膜貫通ドメインとの間にCD28細胞外ドメインをさらに含み、前記CD28細胞外ドメインが、配列番号7のアミノ酸配列を含む、請求項1に記載の抗CD38キメラ抗原受容体(CAR)構築物。
- 前記膜貫通ドメインが、配列番号8のアミノ酸配列を含むCD28膜貫通ドメインである、請求項1に記載の抗CD38キメラ抗原受容体(CAR)構築物。
- 前記細胞内ドメインが、配列番号9のアミノ酸配列を含むCD28細胞内ドメインおよび配列番号10のアミノ酸配列を含むCD3−ゼータ細胞内ドメインを含む、請求項1に記載の抗CD38キメラ抗原受容体(CAR)構築物。
- 配列番号20のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む、請求項1に記載の抗CD38キメラ抗原受容体(CAR)構築物。
- i)配列番号1のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む重鎖可変(VH)ドメインを含み、配列番号3のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む軽鎖可変(VL)ドメインを含む、CD38に結合する抗原結合性タンパク質;
ii)膜貫通ドメイン;および
iii)細胞内ドメイン
を含む抗CD38キメラ抗原受容体(CAR)構築物を発現する宿主細胞または宿主細胞の集団であって、
前記宿主細胞または宿主細胞の集団が、前記抗CD38 CAR構築物をコードする核酸に作動可能に連結した発現ベクターで形質導入され、
前記発現ベクターが、前記宿主細胞における前記抗CD38 CAR構築物の発現を指示する、宿主細胞または宿主細胞の集団。 - iv)配列番号1のアミノ酸配列で示されるCDRを含む重鎖可変(VH)ドメインを含み、配列番号3のアミノ酸配列で示されるCDRを含む軽鎖可変(VL)ドメインを含む、CD38に結合する抗原結合性タンパク質;
v)膜貫通ドメイン;および
vi)細胞内ドメイン
を含む抗CD38キメラ抗原受容体(CAR)構築物を発現する宿主細胞または宿主細胞の集団であって、
前記宿主細胞または宿主細胞の集団が、前記抗CD38 CAR構築物をコードする核酸に作動可能に連結した発現ベクターで形質導入され、
前記発現ベクターが、前記宿主細胞における前記抗CD38キメラCAR構築物の発現を指示する、宿主細胞または宿主細胞の集団。 - 前記発現ベクターが、レトロウイルス発現ベクターまたはレンチウイルス発現ベクターを含む、請求項9または10に記載の宿主細胞または宿主細胞の集団。
- T宿主細胞(またはその集団)、胎盤由来ナチュラルキラー宿主細胞(またはその集団)および臍帯血由来ナチュラルキラー宿主細胞(またはその集団)からなる群から選択される、請求項9または10に記載の宿主細胞または宿主細胞の集団。
- 前記抗CD38キメラ抗原受容体(CAR)構築物が、前記重鎖可変(VH)ドメインと前記軽鎖可変(VL)ドメインとの間にペプチドリンカーをさらに含み、前記ペプチドリンカーが、配列番号5のアミノ酸配列を含む、請求項9または10に記載の宿主細胞または宿主細胞の集団。
- 前記抗原結合性タンパク質が、配列番号12のアミノ酸配列を含む、請求項9に記載の宿主細胞または宿主細胞の集団。
- 前記抗CD38キメラ抗原受容体(CAR)構築物が、前記抗原結合性タンパク質と前記膜貫通ドメインとの間にヒンジ領域をさらに含み、前記ヒンジ領域が、配列番号6のアミノ酸配列を含むCD8ヒンジ領域である、請求項9または10に記載の宿主細胞または宿主細胞の集団。
- 前記抗CD38キメラ抗原受容体(CAR)構築物が、前記抗原結合性タンパク質と前記膜貫通ドメインとの間にCD28細胞外ドメインをさらに含み、前記CD28細胞外ドメインが、配列番号7のアミノ酸配列を含む、請求項9に記載の宿主細胞または宿主細胞の集団。
- 前記膜貫通ドメインが、配列番号8のアミノ酸配列を含むCD28膜貫通ドメインである、請求項9または10に記載の宿主細胞または宿主細胞の集団。
- 前記細胞内ドメインが、配列番号9のアミノ酸配列を含むCD28細胞内ドメインおよび配列番号10のアミノ酸配列を含むCD3−ゼータ細胞内ドメインを含む、請求項9または10に記載の宿主細胞または宿主細胞の集団。
- 前記抗CD38キメラ抗原受容体(CAR)構築物が、配列番号20のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む、請求項9に記載の宿主細胞または宿主細胞の集団。
- 抗CD38 CAR構築物をコードする単離された核酸であって、前記抗CD38構築物が、
a.配列番号1のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む重鎖可変(VH)ドメインを含み、配列番号のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む軽鎖可変(VL)ドメインを含む、細胞外抗原結合性タンパク質;
b.膜貫通ドメイン;および
c.細胞内ドメイン
を含む、単離された核酸。 - 抗CD38 CAR構築物をコードする単離された核酸であって、前記抗CD38構築物が、
a.配列番号1のアミノ酸配列で示されるCDRを含む重鎖可変(VH)ドメインを含み、配列番号のアミノ酸配列で示されるCDRを含む軽鎖可変(VL)ドメインを含む、細胞外抗原結合性タンパク質;
b.膜貫通ドメイン;および
c.細胞内ドメイン
を含む、単離された核酸。 - 前記抗CD38 CAR構築物が、前記重鎖可変(VH)ドメインと前記軽鎖可変(VL)ドメインとの間にペプチドリンカーをさらに含み、前記ペプチドリンカーが、配列番号5のアミノ酸配列を含む、請求項20または21に記載の単離された核酸。
- 前記抗原結合性タンパク質が、配列番号12のアミノ酸配列を含む、請求項20に記載の単離された核酸。
- 前記抗CD38 CAR構築物が、前記抗原結合性タンパク質と前記膜貫通ドメインとの間にヒンジ領域をさらに含み、前記ヒンジ領域が、配列番号6のアミノ酸配列を含むCD8ヒンジ領域である、請求項20または21に記載の単離された核酸。
- 前記抗CD38 CAR構築物が、前記抗原結合性タンパク質と前記膜貫通ドメインとの間にCD28細胞外ドメインをさらに含み、前記CD28細胞外ドメインが、配列番号7のアミノ酸配列を含む、請求項20または21に記載の単離された核酸。
- 前記膜貫通ドメインが、配列番号8のアミノ酸配列を含むCD28膜貫通ドメインである、請求項20または21に記載の単離された核酸。
- 前記細胞内ドメインが、配列番号9のアミノ酸配列を含むCD28細胞内ドメインおよび配列番号10のアミノ酸配列を含むCD3−ゼータ細胞内ドメインを含む、請求項20または21に記載の単離された核酸。
- 配列番号20のアミノ酸配列に対して少なくとも95%同一であるアミノ酸配列を含む、請求項20または21に記載の単離された核酸。
- 前記細胞外抗原結合性タンパク質が、scFvである、請求項20または21に記載の単離された核酸。
- 請求項20または21に記載の核酸を含む発現ベクター。
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PCT/IB2018/058642 WO2019087151A1 (en) | 2017-11-03 | 2018-11-02 | Cd38-directed chimeric antigen receptor constructs |
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BR112021012685A2 (pt) | 2019-01-11 | 2021-12-28 | Omeros Corp | Métodos para tratar câncer, para aumentar o nível de citocinas th1 nas células mononucleares de sangue periférico humanas, para realçar uma resposta imune antitumoral e para estimular e/ou amplificar uma resposta imune em um sujeito mamífero sofrendo de ou em risco de desenvolver câncer ou metástase de câncer, e, composição farmacêutica |
CN114340668A (zh) * | 2019-07-01 | 2022-04-12 | 索伦托药业有限公司 | 结合于cd38和cd3的异源二聚抗体 |
EP3999540A1 (en) * | 2019-07-16 | 2022-05-25 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Antibodies having specificity for cd38 and uses thereof |
US20220273716A1 (en) | 2019-07-25 | 2022-09-01 | Celularity Inc. | Populations of natural killer cells comprising a cd38 chimeric antigen receptor |
CN113663061A (zh) * | 2021-08-04 | 2021-11-19 | 上海优卡迪生物医药科技有限公司 | Cd38在制备car-t药物中的应用 |
CN113893338A (zh) * | 2021-11-04 | 2022-01-07 | 苏州大学附属第一医院 | Cd38 car-t细胞在慢性粒细胞白血病急髓变中的应用 |
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CA3080109A1 (en) | 2019-05-09 |
KR20200076732A (ko) | 2020-06-29 |
US20190135937A1 (en) | 2019-05-09 |
WO2019087151A1 (en) | 2019-05-09 |
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