AU2021239060A1 - GPC3 CAR- T cells secreting IL-18 and methods of making and using the same - Google Patents

GPC3 CAR- T cells secreting IL-18 and methods of making and using the same Download PDF

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Publication number
AU2021239060A1
AU2021239060A1 AU2021239060A AU2021239060A AU2021239060A1 AU 2021239060 A1 AU2021239060 A1 AU 2021239060A1 AU 2021239060 A AU2021239060 A AU 2021239060A AU 2021239060 A AU2021239060 A AU 2021239060A AU 2021239060 A1 AU2021239060 A1 AU 2021239060A1
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immune cell
cell
cells
sequence
car
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Inventor
Young Gyoon CHANG
Jinkyung CHOI
Jiwon Chung
Sun-woo IM
Kwanghee Kim
Byoung S. Kwon
Hye Mi Lee
Jungyun Lee
Seunghyun Lee
Hyuntae SON
Bo-Rim YI
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Eutilex Co Ltd
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Eutilex Co Ltd
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    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/35—Cytokines
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4261—Proteoglycans, e.g. glypican, brevican or CSPG4
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
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    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52—Cytokines; Lymphokines; Interferons
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    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
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    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
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    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
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AU2021239060A 2020-03-18 2021-03-18 GPC3 CAR- T cells secreting IL-18 and methods of making and using the same Pending AU2021239060A1 (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US202062991497P 2020-03-18 2020-03-18
US62/991,497 2020-03-18
US202063004912P 2020-04-03 2020-04-03
US63/004,912 2020-04-03
US202063043401P 2020-06-24 2020-06-24
US63/043,401 2020-06-24
PCT/IB2021/052292 WO2021186395A1 (en) 2020-03-18 2021-03-18 Gpc3 car- t cells secreting il-18 and methods of making and using the same

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AU2021239060A1 true AU2021239060A1 (en) 2022-10-06

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AU2021239060A Pending AU2021239060A1 (en) 2020-03-18 2021-03-18 GPC3 CAR- T cells secreting IL-18 and methods of making and using the same

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US (1) US20230151113A1 (https=)
EP (1) EP4121517A4 (https=)
JP (1) JP7778081B2 (https=)
KR (2) KR20220155589A (https=)
CN (1) CN115461449A (https=)
AU (1) AU2021239060A1 (https=)
CA (1) CA3176125A1 (https=)
WO (1) WO2021186395A1 (https=)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024541076A (ja) * 2021-11-09 2024-11-06 ヤンセン バイオテツク，インコーポレーテツド Ｔ細胞受容体リガンドを特定するためのマイクロ流体共カプセル化デバイス、システム、及び方法
WO2025183436A1 (ko) * 2024-02-27 2025-09-04 (주)이노베이션바이오 Gpc3을 표적으로 하는 키메릭 항원 수용체 및 cd276을 표적으로 하는 키메릭 항원 수용체를 발현하는 면역 이펙터 세포 및 이의 용도

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CL2009000647A1 (es) * 2008-04-04 2010-06-04 Chugai Pharmaceutical Co Ltd Composicion farmaceutica para tratar o prevenir cancer hepatico que comprende una combinacion de un agente quimioterapeutico y un anticuerpo anti-glipicano 3; agente para atenuar un efecto secundario que comprende dicho anticuerpo; metodo para tratar o prevenir un cancer hepatico de un sujeto.
US20150329640A1 (en) * 2012-12-20 2015-11-19 Bluebird Bio, Inc. Chimeric antigen receptors and immune cells targeting b cell malignancies
CN104140974B (zh) * 2013-05-08 2017-09-29 科济生物医药（上海）有限公司 编码gpc‑3嵌合抗原受体蛋白的核酸及表达gpc‑3嵌合抗原受体蛋白的t淋巴细胞
JP2017529851A (ja) * 2014-09-26 2017-10-12 ベイラー カレッジ オブ メディスンＢａｙｌｏｒ Ｃｏｌｌｅｇｅ Ｏｆ Ｍｅｄｉｃｉｎｅ 養子免疫療法のためのグリピカン−３特異的キメラ抗原レセプター
JP7096667B2 (ja) * 2015-07-01 2022-07-06 中外製薬株式会社 Ｇｐｃ３標的治療剤が有効である患者に投与されるｇｐｃ３標的治療剤
JP2019530431A (ja) * 2016-07-26 2019-10-24 テッサ・セラピューティクス・プライベート・リミテッド キメラ抗原受容体
MX2019008221A (es) * 2017-01-10 2019-12-09 Univ Yamaguchi Anticuerpo anti-gpc3.
EP3615574A4 (en) * 2017-04-26 2021-02-24 Eureka Therapeutics, Inc. SPECIFIC GLYPICAN 3 RECOGNIZING CONSTRUCTS AND THEIR USE
US20220127570A1 (en) * 2018-05-03 2022-04-28 Cafa Therapeutics Limited Immune effector cell and use thereof
CN110468105B (zh) * 2018-05-09 2024-03-22 恺兴生命科技(上海)有限公司 表达il-18r结合蛋白的免疫效应细胞
WO2020017479A1 (ja) * 2018-07-17 2020-01-23 ノイルイミューン・バイオテック株式会社 抗ｇｐｃ３一本鎖抗体を含むｃａｒ
CN115667500B (zh) * 2020-03-18 2026-02-06 优特力克斯有限公司 Gpc3 car-t细胞组合物及其制备和使用方法

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WO2021186395A1 (en) 2021-09-23
EP4121517A4 (en) 2024-08-07
US20230151113A1 (en) 2023-05-18
JP7778081B2 (ja) 2025-12-01
CN115461449A (zh) 2022-12-09
JP2023518931A (ja) 2023-05-09
KR20220155589A (ko) 2022-11-23
CA3176125A1 (en) 2021-09-23
EP4121517A1 (en) 2023-01-25
KR20250154516A (ko) 2025-10-28

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