JP2023059873A - T細胞悪性腫瘍の免疫療法のためのcd7発現およびキメラ抗原受容体の遮断 - Google Patents
T細胞悪性腫瘍の免疫療法のためのcd7発現およびキメラ抗原受容体の遮断 Download PDFInfo
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Abstract
Description
本願は、2016年11月22日に出願された米国特許仮出願第62/425,398号、2017年8月10日に出願された同第62/543,696号の利益を主張するものであり、あらゆる目的のためにその全体が参照により明示的に組み込まれる。
配列表
この実施例は、第二世代のCARと組み合わせた新規方法によるCD7発現の遮断を例示し、非常に強力な抗CD7 CAR-T細胞をもたらした。この実用的な戦略は、ETP-ALLを含む高リスクT細胞悪性腫瘍患者に新しい治療法の選択肢を提供する。
概要
序論
材料および方法
考察
参考文献
Claims (53)
- i)局在化ドメインに連結された標的結合分子をコードするヌクレオチド配列を含む核酸であって、前記標的結合分子が、CD7に特異的に結合する第1の抗体である、核酸と、
ii)キメラ抗原受容体(CAR)をコードするヌクレオチド配列を含む核酸であって、前記CARが、4-1BB細胞内シグナル伝達ドメインと、CD3ζ細胞内シグナル伝達ドメインと、CD7に特異的に結合する第2の抗体と、を含む、核酸と、を含む、遺伝子操作免疫細胞。 - CD7に特異的に結合する前記第1の抗体が、第1の単鎖可変フラグメント(scFv)である、請求項1に記載の遺伝子操作免疫細胞。
- CD7に特異的に結合する前記第2の抗体が、第2の単鎖可変フラグメント(scFv)である、請求項1または2に記載の遺伝子操作免疫細胞。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号1のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号2のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項1~3のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号14のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号15のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項1~3のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号16のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号17のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項1~3のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記局在化ドメインが、小胞体(ER)保持配列、ゴルジ体保持配列、プロテアソーム局在化配列、およびCD8α、CD8β、4-1BB、CD28、CD34、CD4、FcεRIγ、CD16、OX40、CD3ζ、CD3ε、CD3γ、CD3δ、TCRα、CD32、CD64、VEGFR2、FAS、またはFGFR2Bに由来する膜貫通ドメイン配列からなる群から選択されるアミノ酸配列を含む、請求項1~4のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記局在化ドメインが、配列番号8または配列番号9のアミノ酸配列を含む小胞体(ER)保持配列を含む、請求項7に記載の遺伝子操作免疫細胞。
- 前記局在化ドメインが、配列番号13のアミノ酸配列を含むCD8αのヒンジおよび膜貫通ドメイン配列に由来する膜貫通ドメイン配列を含む、請求項7に記載の遺伝子操作細胞。
- 前記4-1BB細胞内シグナル伝達ドメインが、配列番号3のアミノ酸配列を含み、前記CD3ζ細胞内シグナル伝達ドメインが、配列番号4のアミノ酸配列を含む、請求項1~9のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記CARが、ヒンジおよび膜貫通ドメインをさらに含む、請求項1~10のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記ヒンジおよび膜貫通ドメインが、配列番号10のアミノ酸配列を含む、請求項11に記載の遺伝子操作免疫細胞。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号1のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号2のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項1~12のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号14のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号15のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項1~12のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号16のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号17のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項1~12のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記遺伝子操作細胞が、遺伝子操作T細胞、遺伝子操作ナチュラルキラー(NK)細胞、遺伝子操作NK/T細胞、遺伝子操作単球、遺伝子操作マクロファージ、または遺伝子操作樹状細胞である、請求項1~15のいずれか一項に記載の遺伝子操作免疫細胞。
- i)局在化ドメインに連結された標的結合分子であって、前記標的結合分子が、CD7に特異的に結合する第1の抗体である、標的結合分子と、
ii)キメラ抗原受容体(CAR)であって、前記CARが、4-1BB細胞内シグナル伝達ドメインと、CD3ζ細胞内シグナル伝達ドメインと、CD7に特異的に結合する第2の抗体と、を含む、CARと、を含む、遺伝子操作免疫細胞。 - CD7に特異的に結合する前記第1の抗体が、第1の単鎖可変フラグメント(scFv)である、請求項17に記載の遺伝子操作免疫細胞。
- CD7に特異的に結合する前記第2の抗体が、第2の単鎖可変フラグメント(scFv)である、請求項17または18に記載の遺伝子操作免疫細胞。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号1のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号2のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項17~19のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号14のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号15のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項17~19のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号16のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号17のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項17~19のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記局在化ドメインが、小胞体(ER)保持配列、ゴルジ体保持配列、プロテアソーム局在化配列、およびCD8α、CD8β、4-1BB、CD28、CD34、CD4、FcεRIγ、CD16、OX40、CD3ζ、CD3ε、CD3γ、CD3δ、TCRα、CD32、CD64、VEGFR2、FAS、またはFGFR2Bに由来する膜貫通ドメイン配列からなる群から選択されるアミノ酸配列を含む、請求項17~19のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記局在化ドメインが、配列番号8または配列番号9のアミノ酸配列を含む小胞体(ER)保持配列を含む、請求項23に記載の遺伝子操作免疫細胞。
- 前記局在化ドメインが、配列番号13のアミノ酸配列を含むCD8αのヒンジおよび膜貫通ドメイン配列に由来する膜貫通ドメイン配列を含む、請求項23に記載の遺伝子操作免疫細胞。
- 前記4-1BB細胞内シグナル伝達ドメインが、配列番号3のアミノ酸配列を含み、前記CD3ζ細胞内シグナル伝達ドメインが、配列番号4のアミノ酸配列を含む、請求項17~25のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記CARが、ヒンジおよび膜貫通ドメインをさらに含む、請求項17~26のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記ヒンジおよび膜貫通ドメインが、配列番号10のアミノ酸配列を含む、請求項27に記載の遺伝子操作免疫細胞。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号1のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号2のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項17~28のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号14のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号15のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項17~28のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号16のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号17のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項17~28のいずれか一項に記載の遺伝子操作免疫細胞。
- 前記遺伝子操作細胞が、遺伝子操作T細胞、遺伝子操作ナチュラルキラー(NK)細胞、遺伝子操作NK/T細胞、遺伝子操作単球、遺伝子操作マクロファージ、または遺伝子操作樹状細胞である、請求項17~31のいずれか一項に記載の遺伝子操作免疫細胞。
- 請求項1~32のいずれか一項に記載の前記遺伝子操作免疫細胞と、薬学的に許容される担体と、を含む、医薬組成物。
- 請求項1~32のいずれか一項に記載の前記遺伝子操作免疫細胞を作製する方法であって、前記方法が、
i)免疫細胞に、
a)局在化ドメインに連結された標的結合分子をコードするヌクレオチド配列を含む第1の核酸であって、前記標的結合分子が、CD7に特異的に結合する第1の抗体である、第1の核酸と、
b)キメラ抗原受容体(CAR)をコードするヌクレオチド配列を含む第2の核酸であって、前記CARが、4-1BB細胞内シグナル伝達ドメインと、CD3ζ細胞内シグナル伝達ドメインと、CD7に特異的に結合する第2の抗体と、を含む、第2の核酸と、を導入することと、
ii)前記局在化ドメインに連結された前記標的結合分子および前記CARを含む遺伝子操作免疫細胞を単離することと、を含む、方法。 - 治療を必要とする被験体の癌を治療する方法であって、治療量の遺伝子操作免疫細胞を前記被験体に投与することと、それによって治療を必要とする被験体の癌を治療することと、を含み、
前記遺伝子操作免疫細胞が、
i)局在化ドメインに連結された標的結合分子をコードするヌクレオチド配列を含む核酸であって、前記標的結合分子が、CD7に特異的に結合する第1の抗体である、核酸と、
ii)キメラ抗原受容体(CAR)をコードするヌクレオチド配列を含む核酸であって、前記CARが、4-1BB細胞内シグナル伝達ドメインと、CD3ζ細胞内シグナル伝達ドメインと、CD7に特異的に結合する第2の抗体と、を含む、核酸と、を含む、方法。 - CD7に特異的に結合する前記第1の抗体が、第1の単鎖可変フラグメント(scFv)である、請求項35に記載の方法。
- CD7に特異的に結合する前記第2の抗体が、第2の単鎖可変フラグメント(scFv)である、請求項35または36に記載の方法。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号1のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号2のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項35~37のいずれか一項に記載の方法。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号14のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号15のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項35~37のいずれか一項に記載の方法。
- 前記第1の単鎖可変フラグメント(scFv)が、配列番号16のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号17のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項35~37のいずれか一項に記載の方法。
- 前記局在化ドメインが、小胞体(ER)保持配列、ゴルジ体保持配列、プロテアソーム局在化配列、およびCD8α、CD8β、4-1BB、CD28、CD34、CD4、FcεRIγ、CD16、OX40、CD3ζ、CD3ε、CD3γ、CD3δ、TCRα、CD32、CD64、VEGFR2、FAS、またはFGFR2Bに由来する膜貫通ドメイン配列からなる群から選択されるアミノ酸配列を含む、請求項35~38のいずれか一項に記載の方法。
- 前記局在化ドメインが、配列番号8または配列番号9のアミノ酸配列を含む小胞体(ER)保持配列を含む、請求項41に記載の方法。
- 前記局在化ドメインが、配列番号13のアミノ酸配列を含むCD8αのヒンジおよび膜貫通ドメイン配列に由来する膜貫通ドメイン配列を含む、請求項41に記載の方法。
- 前記4-1BB細胞内シグナル伝達ドメインが、配列番号3のアミノ酸配列を含み、前記CD3ζ細胞内シグナル伝達ドメインが、配列番号4のアミノ酸配列を含む、請求項35~43のいずれか一項に記載の方法。
- 前記CARが、ヒンジおよび膜貫通ドメインをさらに含む、請求項35~44のいずれか一項に記載の方法。
- 前記ヒンジおよび膜貫通ドメインが、配列番号10のアミノ酸配列を含む、請求項45に記載の方法。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号1のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号2のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項35~46のいずれか一項に記載の方法。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号14のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号15のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項35~46のいずれか一項に記載の方法。
- 前記第2の単鎖可変フラグメント(scFv)が、配列番号16のアミノ酸配列に対して少なくとも90%の配列同一性を有する重鎖可変ドメインと、配列番号17のアミノ酸配列に対して少なくとも90%の配列同一性を有する軽鎖可変ドメインと、を含む、請求項35~46のいずれか一項に記載の方法。
- 前記遺伝子操作細胞が、遺伝子操作T細胞、遺伝子操作ナチュラルキラー(NK)細胞、遺伝子操作NK/T細胞、遺伝子操作単球、遺伝子操作マクロファージ、または遺伝子操作樹状細胞である、請求項35~49のいずれか一項に記載の方法。
- 前記遺伝子操作免疫細胞が、静脈内注入、動脈内注入、腹腔内注入、腫瘍への直接注入および/または手術後の腫瘍床の灌流、人工足場における腫瘍部位への移植、または髄腔内投与によって前記被験体に投与される、請求項35~50のいずれか一項に記載の方法。
- 前記癌が、T細胞悪性腫瘍である、請求項35~51のいずれか一項に記載の方法。
- 前記T細胞悪性腫瘍が、早期T細胞前駆体急性リンパ芽球性白血病(ETP-ALL)である、請求項52に記載の方法。
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Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10765699B2 (en) | 2015-02-06 | 2020-09-08 | National University Of Singapore | Methods for enhancing efficacy of therapeutic immune cells |
MX2018002943A (es) | 2015-09-09 | 2018-09-28 | Monolith Mat Inc | Grafeno circular de pocas capas. |
EP3545082A4 (en) | 2016-11-22 | 2020-07-01 | National University of Singapore | BLOCKING OF CD7 EXPRESSION AND CHIMERIC ANTIGEN RECEPTORS FOR THE IMMUNOTHERAPY OF T-CELL MALIGNANCIES |
US10227576B1 (en) | 2018-06-13 | 2019-03-12 | Caribou Biosciences, Inc. | Engineered cascade components and cascade complexes |
EP3743512A4 (en) * | 2018-10-31 | 2021-12-01 | Nantkwest, Inc. | ELIMINATION OF CD19 POSITIVE LYMPHOID MALIGNACIES BY NK CELLS EXPRESSING CD19-CAR |
US20210395779A1 (en) * | 2018-11-14 | 2021-12-23 | Medisix Therapeutics Pte Ltd. | Two-gene vectors for generating car-t cells and uses thereof |
CN109652379B (zh) * | 2018-12-29 | 2022-08-16 | 博生吉医药科技(苏州)有限公司 | Cd7嵌合抗原受体修饰的nk-92mi细胞及其应用 |
AU2020270298A1 (en) | 2019-05-07 | 2021-12-23 | Gracell Biotechnologies (Shanghai) Co., Ltd. | Engineered immune cell targeting BCMA and use thereof |
GB201914611D0 (en) * | 2019-10-09 | 2019-11-20 | Autolus Ltd | Engineered immune cell |
GB2605514A (en) * | 2019-10-11 | 2022-10-05 | Univ Leland Stanford Junior | Recombinant polypeptides for regulatable cellular localization |
AU2020388690A1 (en) * | 2019-11-20 | 2022-06-09 | Cartherics Pty. Ltd. | Method for providing immune cells with enhanced function |
WO2021118873A1 (en) * | 2019-12-09 | 2021-06-17 | St. Jude Children's Research Hospital, Inc. | Method for preparing cd7-negative, cd3-positive t cells |
US20210253712A1 (en) * | 2020-01-30 | 2021-08-19 | ST Phi Therapeutics | Universal T Cells and the Method of Use Thereof |
CN114525259A (zh) * | 2020-11-03 | 2022-05-24 | 南京北恒生物科技有限公司 | 靶向cd7的嵌合抗原受体及其用途 |
CN112300282A (zh) * | 2020-11-03 | 2021-02-02 | 南京北恒生物科技有限公司 | 靶向cd7的人源化抗体及其用途 |
WO2022104109A1 (en) | 2020-11-13 | 2022-05-19 | Catamaran Bio, Inc. | Genetically modified natural killer cells and methods of use thereof |
CA3198996A1 (en) | 2020-11-24 | 2022-06-02 | Matthew T. Burger | Bcl-xl inhibitor antibody-drug conjugates and methods of use thereof |
CN115947852A (zh) * | 2021-01-12 | 2023-04-11 | 上海雅科生物科技有限公司 | 靶向cd7的工程化免疫细胞、嵌合抗原受体、cd7阻断分子及应用 |
KR20230137923A (ko) * | 2021-02-03 | 2023-10-05 | 바이오헝 테라퓨틱스 리미티드 | 신규한 키메라 항원 수용체 및 이의 용도 |
CN115044617B (zh) * | 2021-03-08 | 2024-08-13 | 河北森朗生物科技有限公司 | Car t细胞的制备方法、car t细胞及其应用 |
CN112980800A (zh) * | 2021-03-08 | 2021-06-18 | 河北森朗生物科技有限公司 | Car-t细胞、其构建方法及其应用 |
CN112662631B (zh) * | 2021-03-16 | 2021-06-29 | 合源生物科技(天津)有限公司 | 一种car-t细胞灌流培养方法 |
CN114591444B (zh) * | 2021-06-08 | 2024-09-24 | 北京美康基免生物科技有限公司 | 一种基于cd7的人源化嵌合抗原受体及其应用 |
WO2023133595A2 (en) | 2022-01-10 | 2023-07-13 | Sana Biotechnology, Inc. | Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses |
WO2023155852A1 (zh) * | 2022-02-17 | 2023-08-24 | 上海优替济生生物医药有限公司 | 经修饰的免疫效应细胞及其用途 |
CN114560943B (zh) * | 2022-02-28 | 2022-12-16 | 先进生物(苏州)有限公司 | Cd7-car-t细胞及其制备方法和应用 |
WO2023185256A1 (zh) * | 2022-03-29 | 2023-10-05 | 中国医学科学院血液病医院(中国医学科学院血液学研究所) | 特异性结合cd7的抗体及其在制备嵌合抗原受体中的应用 |
CN117004603A (zh) * | 2022-04-28 | 2023-11-07 | 南京北恒生物科技有限公司 | 一种cd7基因被敲除的工程化免疫细胞及其用途 |
WO2023225359A1 (en) | 2022-05-20 | 2023-11-23 | Novartis Ag | Antibody-drug conjugates of antineoplastic compounds and methods of use thereof |
WO2023223097A1 (en) | 2022-05-20 | 2023-11-23 | Novartis Ag | Antibody drug conjugates |
WO2024040195A1 (en) | 2022-08-17 | 2024-02-22 | Capstan Therapeutics, Inc. | Conditioning for in vivo immune cell engineering |
CN116179495A (zh) * | 2022-11-28 | 2023-05-30 | 上海恩凯细胞技术有限公司 | 转基因免疫细胞及其应用 |
WO2024119157A1 (en) | 2022-12-02 | 2024-06-06 | Sana Biotechnology, Inc. | Lipid particles with cofusogens and methods of producing and using the same |
Family Cites Families (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2018248A1 (en) | 1989-06-07 | 1990-12-07 | Clyde W. Shearman | Monoclonal antibodies against the human alpha/beta t-cell receptor, their production and use |
US5885573A (en) | 1993-06-01 | 1999-03-23 | Arch Development Corporation | Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies |
CA2304208A1 (en) | 1997-09-19 | 1999-03-25 | Dana-Farber Cancer Institute, Inc. | Intrabody-mediated control of immune reactions |
WO2001029058A1 (en) | 1999-10-15 | 2001-04-26 | University Of Massachusetts | Rna interference pathway genes as tools for targeted genetic interference |
US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
WO2001096584A2 (en) | 2000-06-12 | 2001-12-20 | Akkadix Corporation | Materials and methods for the control of nematodes |
AU2002220265A1 (en) * | 2000-11-03 | 2002-05-15 | University Of Vermont And State Agricultural College | Compositions for inhibiting grb7 |
WO2003051926A2 (en) | 2001-12-14 | 2003-06-26 | Friedrich-Alexander-Universitaet Erlangen-Nuernberg | Anti-cd7 immunotoxin as fusion protein |
WO2005017163A2 (en) | 2003-08-15 | 2005-02-24 | Imperial College Innovations Limited | Phenotypic knockout of cell-surface proteins |
US7435596B2 (en) | 2004-11-04 | 2008-10-14 | St. Jude Children's Research Hospital, Inc. | Modified cell line and method for expansion of NK cell |
US20130266551A1 (en) | 2003-11-05 | 2013-10-10 | St. Jude Children's Research Hospital, Inc. | Chimeric receptors with 4-1bb stimulatory signaling domain |
EP1791868B1 (en) | 2004-07-01 | 2011-02-23 | Novo Nordisk A/S | Antibodies binding to receptors kir2dl1, -2, 3 but not kir2ds4 and their therapeutic use |
WO2006047637A1 (en) | 2004-10-27 | 2006-05-04 | Medimmune, Inc. | Use of modulators of epha2 and ephrina1 for the treatment and prevention of infections |
US20070036773A1 (en) | 2005-08-09 | 2007-02-15 | City Of Hope | Generation and application of universal T cells for B-ALL |
EP1951757B1 (en) | 2005-10-06 | 2014-05-14 | Xencor, Inc. | Optimized anti-cd30 antibodies |
JP5726417B2 (ja) | 2007-03-01 | 2015-06-03 | シムフォゲン・アクティーゼルスカブSymphogen A/S | 組み換え抗上皮成長因子受容体抗体組成物 |
JP5518711B2 (ja) | 2007-09-07 | 2014-06-11 | アジェンシス,インコーポレイテッド | 24p4c12タンパク質に結合する抗体および関連分子 |
CN101952317B (zh) | 2008-01-24 | 2015-07-22 | 诺沃-诺迪斯克有限公司 | 人化抗-人nkg2a单克隆抗体 |
US8580714B2 (en) | 2009-10-14 | 2013-11-12 | Janssen Biotech, Inc. | Methods of affinity maturing antibodies |
US9273283B2 (en) | 2009-10-29 | 2016-03-01 | The Trustees Of Dartmouth College | Method of producing T cell receptor-deficient T cells expressing a chimeric receptor |
KR102243575B1 (ko) | 2010-12-09 | 2021-04-22 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 암을 치료하기 위한 키메릭 항원 수용체 변형 t 세포의 용도 |
WO2013126712A1 (en) | 2012-02-22 | 2013-08-29 | The Trustees Of The University Of Pennsylvania | Compositions and methods for generating a persisting population of t cells useful for the treatment of cancer |
DE202013012241U1 (de) | 2012-05-25 | 2016-01-18 | Emmanuelle Charpentier | Zusammensetzungen für die durch RNA gesteuerte Modifikation einer Ziel-DNA und für die durch RNA gesteuerte Modulation der Transkription |
DK2906684T3 (da) | 2012-10-10 | 2020-09-28 | Sangamo Therapeutics Inc | T-celle-modificerende forbindelser og anvendelser deraf |
US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
WO2014093831A2 (en) * | 2012-12-14 | 2014-06-19 | Thomson Reuters (Markets) Llc | Dynamic function builder |
KR101521224B1 (ko) * | 2012-12-20 | 2015-05-19 | 한양대학교 산학협력단 | T 세포 특이적인 인간화 단일조각항체 전달체 |
KR102160322B1 (ko) | 2012-12-27 | 2020-09-25 | 아두로 바이오테크, 인코포레이티드 | 항원 서열의 리스테리아 발현을 용이하게 하는 신호 펩타이드 융합 상대 및 이의 제조방법 및 용도 |
KR20220100093A (ko) | 2013-02-06 | 2022-07-14 | 안트로제네시스 코포레이션 | 개선된 특이성을 갖는 변경된 t 림프구 |
PT2961831T (pt) | 2013-02-26 | 2020-10-12 | Memorial Sloan Kettering Cancer Center | Composições e métodos para imunoterapêutica |
EP3004337B1 (en) | 2013-05-29 | 2017-08-02 | Cellectis | Methods for engineering t cells for immunotherapy by using rna-guided cas nuclease system |
EP3858379A1 (en) | 2013-11-21 | 2021-08-04 | Autolus Limited | Cell |
EP3105317B1 (en) | 2014-02-14 | 2018-09-19 | Cellectis | Cells for immunotherapy engineered for targeting antigen present both on immune cells and pathological cells |
GB201405845D0 (en) | 2014-04-01 | 2014-05-14 | Ucl Business Plc | Signalling system |
EP3169773B1 (en) | 2014-07-15 | 2023-07-12 | Juno Therapeutics, Inc. | Engineered cells for adoptive cell therapy |
CA2963327A1 (en) | 2014-10-07 | 2016-04-14 | Cellectis | Method for modulating car-induced immune cells activity |
KR102376244B1 (ko) | 2014-12-24 | 2022-03-21 | 오토러스 리미티드 | 세포 |
US10765699B2 (en) | 2015-02-06 | 2020-09-08 | National University Of Singapore | Methods for enhancing efficacy of therapeutic immune cells |
KR102632082B1 (ko) * | 2015-02-27 | 2024-02-02 | 아이셀 진 테라퓨틱스 엘엘씨 | 혈액 악성종양을 표적으로 하는 키메라 항원 수용체(car), 조성물 및 이의 용도 |
JP6336684B2 (ja) | 2015-03-02 | 2018-06-06 | イノベイティブ セルラー セラピューティクス シーオー.,エルティディ.Innovative Cellular Therapeutics Co.,Ltd. | Pd−l1によって誘導される免疫寛容の低減 |
US20170119820A1 (en) | 2015-07-31 | 2017-05-04 | Regents Of The University Of Minnesota | Modified cells and methods of therapy |
US20180371052A1 (en) * | 2015-12-22 | 2018-12-27 | Icell Gene Therapeutics Llc | Chimeric antigen receptors and enhancement of anti-tumor activity |
EP3423482A1 (en) | 2016-03-04 | 2019-01-09 | Novartis AG | Cells expressing multiple chimeric antigen receptor (car) molecules and uses therefore |
US11390658B2 (en) | 2016-06-06 | 2022-07-19 | St. Jude Children's Research Hospital | Anti-CD7 chimeric antigen receptor and method of use thereof |
CA2937157A1 (en) | 2016-07-25 | 2018-01-25 | Ucl Business Plc | Protein-based t-cell receptor knockdown |
SG11201900772YA (en) | 2016-08-03 | 2019-02-27 | John Dipersio | Gene editing of car-t cells for the treatment of t cell malignancies with chimeric antigen receptors |
EP3545082A4 (en) | 2016-11-22 | 2020-07-01 | National University of Singapore | BLOCKING OF CD7 EXPRESSION AND CHIMERIC ANTIGEN RECEPTORS FOR THE IMMUNOTHERAPY OF T-CELL MALIGNANCIES |
US20190038733A1 (en) | 2017-08-10 | 2019-02-07 | National University Of Singapore | T cell receptor-deficient chimeric antigen receptor t-cells and methods of use thereof |
US20210395779A1 (en) | 2018-11-14 | 2021-12-23 | Medisix Therapeutics Pte Ltd. | Two-gene vectors for generating car-t cells and uses thereof |
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