JP2018532432A5 - - Google Patents
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- JP2018532432A5 JP2018532432A5 JP2018543073A JP2018543073A JP2018532432A5 JP 2018532432 A5 JP2018532432 A5 JP 2018532432A5 JP 2018543073 A JP2018543073 A JP 2018543073A JP 2018543073 A JP2018543073 A JP 2018543073A JP 2018532432 A5 JP2018532432 A5 JP 2018532432A5
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- chimeric receptor
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- antigen
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562251590P | 2015-11-05 | 2015-11-05 | |
| US62/251,590 | 2015-11-05 | ||
| PCT/US2016/060736 WO2017079705A1 (en) | 2015-11-05 | 2016-11-04 | Chimeric receptors containing traf-inducing domains and related compositions and methods |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2018532432A JP2018532432A (ja) | 2018-11-08 |
| JP2018532432A5 true JP2018532432A5 (OSRAM) | 2019-12-12 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018543073A Ceased JP2018532432A (ja) | 2015-11-05 | 2016-11-04 | Ｔｒａｆ誘導ドメインを含有するキメラ受容体ならびに関連する組成物および方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20180319862A1 (OSRAM) |
| EP (1) | EP3370762A1 (OSRAM) |
| JP (1) | JP2018532432A (OSRAM) |
| KR (1) | KR20180082493A (OSRAM) |
| CN (1) | CN108472346A (OSRAM) |
| AU (1) | AU2016349724B2 (OSRAM) |
| BR (1) | BR112018008442A2 (OSRAM) |
| CA (1) | CA3002990A1 (OSRAM) |
| MA (1) | MA44314A (OSRAM) |
| MX (1) | MX2018005618A (OSRAM) |
| WO (1) | WO2017079705A1 (OSRAM) |
Families Citing this family (58)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9511092B2 (en) | 2013-01-28 | 2016-12-06 | St. Jude Children's Research Hospital, Inc. | Chimeric receptor with NKG2D specificity for use in cell therapy against cancer and infectious disease |
| AU2015259877B2 (en) | 2014-05-15 | 2021-02-25 | National University Of Singapore | Modified natural killer cells and uses thereof |
| SI3240805T1 (sl) | 2014-12-15 | 2025-04-30 | The Regents Of The University Of California | Bispecifični or-gate himerni antigenski receptor, odziv na cd19 in cd20 |
| US10973914B2 (en) | 2015-02-20 | 2021-04-13 | Ohio State Innovation Foundation | Bivalent antibody directed against NKG2D and tumor associated antigens |
| JP6879932B2 (ja) | 2015-04-06 | 2021-06-02 | サイトイミューン セラピューティクス， インコーポレイテッドＣｙｔｏｉｍｍｕｎｅ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｌｌｃ | 神経膠芽腫のためのｅｇｆｒ指向ｃａｒ療法 |
| CA3035080A1 (en) | 2016-09-27 | 2018-04-05 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules |
| AU2017384900B2 (en) | 2016-12-28 | 2020-12-10 | GC Cell Corporation | Chimeric antigen receptor and natural killer cells expressing same |
| BR112019019917A2 (pt) | 2017-03-27 | 2020-04-22 | Nat Univ Singapore | receptores quiméricos nkg2d truncados e seus usos em imunoterapia de células exterminadoras naturais |
| WO2018182511A1 (en) | 2017-03-27 | 2018-10-04 | National University Of Singapore | Stimulatory cell lines for ex vivo expansion and activation of natural killer cells |
| CN107177632B (zh) * | 2017-05-27 | 2020-02-07 | 上海优卡迪生物医药科技有限公司 | 一种基于octs技术的髓系白血病car-t治疗载体及其构建方法和应用 |
| RU2020113627A (ru) * | 2017-09-20 | 2021-10-20 | Нексиммьюн, Инк. | Композиции клеток, содержащие антигенспецифические т-клетки, для адоптивной терапии |
| AU2018341244A1 (en) | 2017-09-26 | 2020-03-05 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules and methods of use |
| EP3687575A4 (en) * | 2017-09-29 | 2021-06-30 | National Health Research Institutes | METHODS AND COMPOSITIONS FOR INCREASING SURVIVAL AND FUNCTIONALITY OF ANTITUMOR AND ANTIVIRUS T CELLS |
| US11649294B2 (en) | 2017-11-14 | 2023-05-16 | GC Cell Corporation | Anti-HER2 antibody or antigen-binding fragment thereof, and chimeric antigen receptor comprising same |
| CN111655732B (zh) * | 2017-11-14 | 2023-09-12 | Gc细胞治疗 | 抗her2抗体或其抗原结合片段及包含其的嵌合抗原受体 |
| AU2019219454A1 (en) | 2018-02-09 | 2020-08-27 | National University Of Singapore | Activating chimeric receptors and uses thereof in natural killer cell immunotherapy |
| AU2019233917A1 (en) * | 2018-03-16 | 2020-09-17 | Cytoimmune Therapeutics, Inc. | Bispecific antibody car cell immunotherapy |
| WO2019191334A1 (en) | 2018-03-28 | 2019-10-03 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
| CN112218887B (zh) | 2018-03-28 | 2025-12-12 | 森罗治疗控股公司 | 细胞免疫疗法组合物及其用途 |
| SG11202008976YA (en) | 2018-04-02 | 2020-10-29 | Nat Univ Singapore | Neutralization of human cytokines with membrane-bound anti-cytokine non-signaling binders expressed in immune cells |
| US20210177903A1 (en) * | 2018-08-07 | 2021-06-17 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Car t-cells for the treatment of bone metastatic cancer |
| WO2020033464A1 (en) | 2018-08-07 | 2020-02-13 | H. Lee Moffitt Cancer Center And Research Institute Inc. | Car t-cells for the treatment of bone metastatic cancer |
| JP7560882B2 (ja) | 2018-08-29 | 2024-10-03 | ナショナル ユニヴァーシティー オブ シンガポール | 遺伝子修飾免疫細胞の生存及び増加を特異的に刺激するための方法 |
| WO2020051562A2 (en) | 2018-09-07 | 2020-03-12 | Beam Therapeutics Inc. | Compositions and methods for improving base editing |
| JP7520818B2 (ja) | 2018-09-13 | 2024-07-23 | ンカルタ・インコーポレイテッド | 腫瘍を治療するためのナチュラルキラー細胞組成物および免疫療法の方法 |
| EP3872087B1 (en) * | 2018-10-26 | 2024-09-25 | Shinshu University | High-efficiency method for producing genetically modified cells |
| CA3118757A1 (en) * | 2018-11-08 | 2020-05-14 | Neximmune, Inc. | T cell compositions with improved phenotypic properties |
| GB201900858D0 (en) * | 2019-01-22 | 2019-03-13 | Price Nicola Kaye | Receptors providing targeted costimulation for adoptive cell therapy |
| AU2020224160A1 (en) * | 2019-02-21 | 2021-08-26 | John M. LUK | Artificial immunosurveillance chimeric antigen receptor (AI-CAR) and cells expressing the same |
| CN118546959A (zh) | 2019-03-05 | 2024-08-27 | 恩卡尔塔公司 | Cd19定向性嵌合抗原受体及其在免疫疗法中的用途 |
| US20220265715A1 (en) * | 2019-07-24 | 2022-08-25 | Eureka Therapeutics, Inc. | Chimeric antigen receptor t cells and uses thereof |
| WO2021019706A1 (ja) * | 2019-07-31 | 2021-02-04 | 国立大学法人信州大学 | Ｃａｒ発現免疫細胞を含む細胞集団の製造方法 |
| CN112390894A (zh) * | 2019-08-12 | 2021-02-23 | 广东东阳光药业有限公司 | 嵌合抗原受体及其应用 |
| JP2022547967A (ja) * | 2019-09-11 | 2022-11-16 | ミガル ガリラヤ リサーチ インスティテュート リミテッド | Ｃｄ４０細胞質ドメインを含むキメラ抗原レセプター及びその使用 |
| CN112251452A (zh) * | 2019-10-22 | 2021-01-22 | 上海斯丹赛生物技术有限公司 | Til/tcr-t细胞治疗平台 |
| IL293716A (en) | 2019-12-11 | 2022-08-01 | A2 Biotherapeutics Inc | Lilrb1-based chimeric antigen receptor |
| CN115087666B (zh) * | 2020-02-13 | 2023-10-03 | 北京艺妙神州医药科技有限公司 | 嵌合抗原受体的优化 |
| CN113402612A (zh) * | 2020-03-17 | 2021-09-17 | 西比曼生物科技（香港）有限公司 | 靶向cd19和cd20的联合嵌合抗原受体及其应用 |
| CN111849910B (zh) | 2020-05-27 | 2021-06-15 | 南京北恒生物科技有限公司 | 工程化免疫细胞及其用途 |
| EP4182336A1 (en) * | 2020-07-17 | 2023-05-24 | Instil Bio (Uk) Limited | Chimeric molecules providing targeted costimulation for adoptive cell therapy |
| KR20230088333A (ko) * | 2020-07-17 | 2023-06-19 | 인스틸 바이오 유케이 리미티드 | 입양 세포 요법을 위한 표적화된 공동자극을 제공하는 수용체 |
| IL300500A (en) | 2020-08-20 | 2023-04-01 | A2 Biotherapeutics Inc | Preparations and methods for the treatment of mesothelin positive cancer |
| JP7621461B2 (ja) | 2020-08-20 | 2025-01-24 | エー２ バイオセラピューティクス， インコーポレイテッド | Ｅｇｆｒ陽性がんを治療するための組成物及び方法 |
| MX2023002017A (es) | 2020-08-20 | 2023-04-28 | A2 Biotherapeutics Inc | Composiciones y métodos para tratar cánceres positivos para ceacam. |
| US20230312673A1 (en) * | 2020-09-02 | 2023-10-05 | The Regents Of The University Of California | Chimeric receptors with diverse co-regulatory sequences |
| US20240000938A1 (en) * | 2020-11-24 | 2024-01-04 | A2 Biotherapeutics, Inc. | Adoptive cell therapy for treatment of cancer associated with loss of heterozygosity |
| BR112023022765A2 (pt) | 2021-05-05 | 2024-01-02 | Immatics Biotechnologies Gmbh | Proteínas de ligação ao antígeno que ligam especificamente o prame |
| EP4355340A4 (en) | 2021-06-16 | 2025-05-21 | Instil Bio, Inc. | RECEPTORS FOR TARGETED COSTIMULATION FOR ADOPTIVE CELL THERAPY |
| US20240252636A1 (en) * | 2021-06-24 | 2024-08-01 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Dual egfr-muci chimeric cantigen receptor t cells |
| EP4370213A4 (en) | 2021-07-16 | 2025-06-04 | Instil Bio (Uk) Limited | Chimeric molecules for targeted costimulation for adoptive cell therapy |
| WO2023020472A1 (en) * | 2021-08-16 | 2023-02-23 | Utc Therapeutics (Shanghai) Co., Ltd. | Mesothelin-targetting antibodies and uses thereof in cancer therapies |
| WO2023190550A1 (ja) * | 2022-03-29 | 2023-10-05 | 学校法人自治医科大学 | 遺伝子改変免疫細胞療法のための選択的制御遺伝子（ｓｒｇ）システム |
| AU2023243458A1 (en) * | 2022-03-30 | 2024-10-31 | Shoreline Biosciences, Inc. | Chimeric antigen receptors for natural killer cells and uses thereof in immunotherapy |
| JP2025514646A (ja) * | 2022-04-07 | 2025-05-09 | アンスティテュ キュリィ | Ｃｄ４０を有するキメラ抗原受容体で改変された骨髄系細胞及び抗がん治療のためのその使用 |
| JP2025511383A (ja) * | 2022-04-07 | 2025-04-15 | アンスティテュ キュリィ | キメラ抗原受容体で改変された骨髄系細胞及び抗がん治療のためのその使用 |
| WO2024091669A1 (en) * | 2022-10-28 | 2024-05-02 | Ginkgo Bioworks, Inc. | Chimeric antigen receptors comprising an intracellular domain pair |
| CN120712345A (zh) * | 2022-12-30 | 2025-09-26 | 上药生物治疗（香港）有限公司 | 表达趋化因子受体的细胞及其用途 |
| WO2025212519A1 (en) | 2024-04-01 | 2025-10-09 | Moonlight Bio, Inc. | Dll3 binding proteins and uses thereof |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4452773A (en) | 1982-04-05 | 1984-06-05 | Canadian Patents And Development Limited | Magnetic iron-dextran microspheres |
| US4690915A (en) | 1985-08-08 | 1987-09-01 | The United States Of America As Represented By The Department Of Health And Human Services | Adoptive immunotherapy as a treatment modality in humans |
| US4795698A (en) | 1985-10-04 | 1989-01-03 | Immunicon Corporation | Magnetic-polymer particles |
| IN165717B (OSRAM) | 1986-08-07 | 1989-12-23 | Battelle Memorial Institute | |
| US5219740A (en) | 1987-02-13 | 1993-06-15 | Fred Hutchinson Cancer Research Center | Retroviral gene transfer into diploid fibroblasts for gene therapy |
| ES2067018T3 (es) | 1988-12-28 | 1995-03-16 | Stefan Miltenyi | Procedimiento y materiales para la separacion en alto gradiente magnetico de materiales biologicos. |
| US5200084A (en) | 1990-09-26 | 1993-04-06 | Immunicon Corporation | Apparatus and methods for magnetic separation |
| DE4228458A1 (de) | 1992-08-27 | 1994-06-01 | Beiersdorf Ag | Multicistronische Expressionseinheiten und deren Verwendung |
| US5827642A (en) | 1994-08-31 | 1998-10-27 | Fred Hutchinson Cancer Research Center | Rapid expansion method ("REM") for in vitro propagation of T lymphocytes |
| US20020150914A1 (en) | 1995-06-30 | 2002-10-17 | Kobenhavns Universitet | Recombinant antibodies from a phage display library, directed against a peptide-MHC complex |
| DE19608753C1 (de) | 1996-03-06 | 1997-06-26 | Medigene Gmbh | Transduktionssystem und seine Verwendung |
| US6451995B1 (en) | 1996-03-20 | 2002-09-17 | Sloan-Kettering Institute For Cancer Research | Single chain FV polynucleotide or peptide constructs of anti-ganglioside GD2 antibodies, cells expressing same and related methods |
| WO2000014257A1 (en) | 1998-09-04 | 2000-03-16 | Sloan-Kettering Institute For Cancer Research | Fusion receptors specific for prostate-specific membrane antigen and uses thereof |
| AU2472400A (en) | 1998-10-20 | 2000-05-08 | City Of Hope | CD20-specific redirected T cells and their use in cellular immunotherapy of CD20+ malignancies |
| WO2001094944A2 (en) | 2000-06-02 | 2001-12-13 | Memorial Sloan-Kettering Cancer Center | Artificial antigen presenting cells and methods of use thereof |
| ATE338124T1 (de) | 2000-11-07 | 2006-09-15 | Hope City | Cd19-spezifische umgezielte immunzellen |
| US7070995B2 (en) | 2001-04-11 | 2006-07-04 | City Of Hope | CE7-specific redirected immune cells |
| US20090257994A1 (en) | 2001-04-30 | 2009-10-15 | City Of Hope | Chimeric immunoreceptor useful in treating human cancers |
| US7939059B2 (en) | 2001-12-10 | 2011-05-10 | California Institute Of Technology | Method for the generation of antigen-specific lymphocytes |
| US20030170238A1 (en) | 2002-03-07 | 2003-09-11 | Gruenberg Micheal L. | Re-activated T-cells for adoptive immunotherapy |
| US7446190B2 (en) | 2002-05-28 | 2008-11-04 | Sloan-Kettering Institute For Cancer Research | Nucleic acids encoding chimeric T cell receptors |
| US20050129671A1 (en) | 2003-03-11 | 2005-06-16 | City Of Hope | Mammalian antigen-presenting T cells and bi-specific T cells |
| EP2856876B1 (en) | 2007-03-30 | 2018-01-31 | Memorial Sloan-Kettering Cancer Center | Constitutive expression of costimulatory ligands on adoptively transferred T lymphocytes |
| DK2520643T3 (da) | 2007-12-07 | 2020-01-20 | Miltenyi Biotec Bv & Co Kg | Prøvebehandlingssystemer og -fremgangsmåder |
| US8479118B2 (en) | 2007-12-10 | 2013-07-02 | Microsoft Corporation | Switching search providers within a browser search box |
| US20120164718A1 (en) | 2008-05-06 | 2012-06-28 | Innovative Micro Technology | Removable/disposable apparatus for MEMS particle sorting device |
| JP5173594B2 (ja) | 2008-05-27 | 2013-04-03 | キヤノン株式会社 | 管理装置、画像形成装置及びそれらの処理方法 |
| US8822647B2 (en) | 2008-08-26 | 2014-09-02 | City Of Hope | Method and compositions using a chimeric antigen receptor for enhanced anti-tumor effector functioning of T cells |
| CA2779526C (en) | 2009-11-03 | 2022-12-06 | City Of Hope | Truncated epiderimal growth factor receptor (egfrt) for transduced t cell selection |
| PH12013501201A1 (en) * | 2010-12-09 | 2013-07-29 | Univ Pennsylvania | Use of chimeric antigen receptor-modified t cells to treat cancer |
| CN110200997A (zh) | 2011-03-23 | 2019-09-06 | 弗雷德哈钦森癌症研究中心 | 用于细胞免疫治疗的方法和组合物 |
| EA201391449A1 (ru) | 2011-04-01 | 2014-03-31 | Мемориал Слоан-Кеттеринг Кэнсер Сентер | Антитела против пептидов цитозоля |
| US8398282B2 (en) | 2011-05-12 | 2013-03-19 | Delphi Technologies, Inc. | Vehicle front lighting assembly and systems having a variable tint electrowetting element |
| ES2687954T3 (es) | 2011-11-11 | 2018-10-30 | Fred Hutchinson Cancer Research Center | Inmunoterapia de linfocitos T dirigidos a ciclina A1 contra el cáncer |
| EP3594245A1 (en) | 2012-02-13 | 2020-01-15 | Seattle Children's Hospital d/b/a Seattle Children's Research Institute | Bispecific chimeric antigen receptors and therapeutic uses thereof |
| WO2013126726A1 (en) | 2012-02-22 | 2013-08-29 | The Trustees Of The University Of Pennsylvania | Double transgenic t cells comprising a car and a tcr and their methods of use |
| SG11201404284SA (en) * | 2012-02-22 | 2014-10-30 | Univ Pennsylvania | Use of the cd2 signaling domain in second-generation chimeric antigen receptors |
| RU2018130123A (ru) | 2012-05-03 | 2018-11-07 | Фред Хатчинсон Кансэр Рисёч Сентер | Клетка, экспрессирующая t-клеточный рецептор (tcr), для применения в клеточной иммунотерапии |
| IL293944A (en) | 2012-08-20 | 2022-08-01 | Hutchinson Fred Cancer Res | Method and preparations for cellular immunotherapy |
| US10316289B2 (en) | 2012-09-06 | 2019-06-11 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods of producing T memory stem cell populations |
| CN104853766A (zh) | 2012-10-02 | 2015-08-19 | 纪念斯隆-凯特琳癌症中心 | 用于免疫疗法的组合物和方法 |
| WO2014097442A1 (ja) | 2012-12-20 | 2014-06-26 | 三菱電機株式会社 | 車載装置及びプログラム |
| WO2014151960A2 (en) * | 2013-03-14 | 2014-09-25 | Bellicum Pharmaceuticals, Inc. | Methods for controlling t cell proliferation |
| UY35468A (es) | 2013-03-16 | 2014-10-31 | Novartis Ag | Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19 |
| US9108442B2 (en) | 2013-08-20 | 2015-08-18 | Ricoh Company, Ltd. | Image forming apparatus |
| ES2963718T3 (es) * | 2014-01-21 | 2024-04-01 | Novartis Ag | Capacidad presentadora de antígenos de células CAR-T potenciada mediante introducción conjunta de moléculas co-estimuladoras |
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0
- MA MA044314A patent/MA44314A/fr unknown
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2016
- 2016-11-04 KR KR1020187015890A patent/KR20180082493A/ko not_active Ceased
- 2016-11-04 CA CA3002990A patent/CA3002990A1/en not_active Abandoned
- 2016-11-04 US US15/773,540 patent/US20180319862A1/en not_active Abandoned
- 2016-11-04 MX MX2018005618A patent/MX2018005618A/es unknown
- 2016-11-04 EP EP16810123.6A patent/EP3370762A1/en not_active Withdrawn
- 2016-11-04 WO PCT/US2016/060736 patent/WO2017079705A1/en not_active Ceased
- 2016-11-04 JP JP2018543073A patent/JP2018532432A/ja not_active Ceased
- 2016-11-04 CN CN201680077930.4A patent/CN108472346A/zh active Pending
- 2016-11-04 BR BR112018008442A patent/BR112018008442A2/pt not_active Application Discontinuation
- 2016-11-04 AU AU2016349724A patent/AU2016349724B2/en not_active Ceased
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