AU2015306231B2 - Genetically modified mesenchymal stem cells expressing an immune response-stimulating cytokine to attract and/or activate immune cells - Google Patents
Genetically modified mesenchymal stem cells expressing an immune response-stimulating cytokine to attract and/or activate immune cells Download PDFInfo
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| PT3107573T (pt) * | 2014-02-19 | 2019-01-10 | Merck Patent Gmbh | Imunoterapia com il-12 visada ao cancro |
| CN108884440A (zh) | 2016-04-01 | 2018-11-23 | 埃普塞斯有限责任两合公司 | 用于增强免疫疗法的抗肿瘤活性的间充质干细胞 |
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| CN110527696A (zh) * | 2018-06-13 | 2019-12-03 | 中山大学 | 一种IFNβ和FerritinH基因联合修饰的骨髓间充质干细胞及其制备方法和应用 |
| CN108815188A (zh) * | 2018-07-06 | 2018-11-16 | 浙江生创精准医疗科技有限公司 | 包含间充质干细胞制剂与免疫检查点抑制剂的肿瘤治疗组合物、试剂盒及其用途 |
| US20210346430A9 (en) * | 2018-08-26 | 2021-11-11 | Oaiscell Biotechnologies | Method for treating glioblastoma |
| CN112771167B (zh) * | 2018-09-20 | 2025-09-26 | 克莱格医学有限公司 | 表达有趋化因子的细胞及用途 |
| EP3864142A4 (en) * | 2018-10-12 | 2023-07-19 | iCell Gene Therapeutics LLC | CHEMERA ANTIGEN RECEPTORS (CARs), COMPOSITIONS AND METHODS OF USE THEREOF |
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| CN109593725A (zh) * | 2018-12-25 | 2019-04-09 | 河北生命原点生物科技有限公司 | 一种重组间充质干细胞及其应用 |
| US20220128541A1 (en) * | 2019-02-14 | 2022-04-28 | Research Institute At Nationwide Children's Hospital | Use of plasma membrane particles, liposomes, and exosomes to assay immune cell potency |
| CN109762820B (zh) * | 2019-02-18 | 2020-07-28 | 河北佑仁生物科技有限公司 | 一种骨髓间充质干细胞特异性启动元件在干细胞中的应用 |
| EP3946440A4 (en) * | 2019-04-02 | 2023-04-19 | The General Hospital Corporation | Methods to enhance t cell regeneration |
| CN115851605A (zh) * | 2019-04-18 | 2023-03-28 | 上海交通大学 | 间充质干细胞靶向运输趋化因子和细胞因子的免疫疗法 |
| CN111139222B (zh) * | 2019-05-30 | 2020-12-29 | 北京双因生物科技有限公司 | 一种重组间充质干细胞及其制备方法和用途 |
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| WO2021194427A1 (en) * | 2020-03-26 | 2021-09-30 | Agency For Science, Technology And Research | A method and system for introducing one or more exogenous substances into an immune cell |
| BR112022016715A2 (pt) * | 2020-05-27 | 2022-11-16 | Univ Zuerich | Vetores virais que expressam proteínas terapêuticos especificamente em células mieloides e microglia |
| US20230257713A1 (en) * | 2020-07-16 | 2023-08-17 | Shanghai Jiaotong University | Immunotherapy method of targeted chemokine and cytokine delivery by mesenchymal stem cell |
| US20230399622A1 (en) * | 2020-10-16 | 2023-12-14 | Fundació Centre De Regulació Genòmica | Therapy for degenerative disease and tissue damage |
| CN114426953A (zh) * | 2020-10-29 | 2022-05-03 | 未来智人再生医学研究院(广州)有限公司 | 一种表达il-12的多能干细胞衍生物及应用 |
| CN114507643A (zh) * | 2020-10-29 | 2022-05-17 | 未来智人再生医学研究院(广州)有限公司 | 一种表达il-2的多能干细胞衍生物及应用 |
| CN114717232A (zh) * | 2020-12-22 | 2022-07-08 | 未来智人再生医学研究院(广州)有限公司 | 表达irf-1靶向抑制因子的多能干细胞及其衍生物与应用 |
| WO2023274355A1 (zh) * | 2021-07-02 | 2023-01-05 | 上海交通大学 | 改造的间充质干细胞和免疫效应细胞联合治疗肿瘤 |
| WO2023076670A1 (en) * | 2021-11-01 | 2023-05-04 | MAM Holdings of West Florida, L.L.C. | Mesenchymal stem cells for the prevention and targeted treatment of cancer and other disorders |
| CN114480413B (zh) * | 2022-01-14 | 2022-11-04 | 北京贝来生物科技有限公司 | 一种活化肿瘤免疫应答的基因修饰干细胞制备方法 |
| CN115463155B (zh) * | 2022-11-01 | 2023-05-23 | 卡瑞济(北京)生命科技有限公司 | 间充质干细胞的用途 |
| CN117503952B (zh) * | 2022-11-24 | 2025-09-16 | 中国药科大学 | 一种基于血小板的免疫激活系统及其制备方法和应用 |
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| US20250333700A1 (en) * | 2024-02-28 | 2025-10-30 | Gene Solutions Joint Stock Company | Modified k562 feeder cell line expressing factors that enhance the activation and proliferation of natural killer cells and a method for its production |
Citations (2)
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|---|---|---|---|---|
| EP1658853A1 (en) * | 2003-06-27 | 2006-05-24 | Renomedix Institute Inc. | Remedy for internal administration against cranial nerve diseases containing mesenchymal cells as the active ingredient |
| WO2008150368A1 (en) * | 2007-05-24 | 2008-12-11 | Apceth Gmbh & Co. Kg | Cd34 stem cell-related methods and compositions |
Family Cites Families (13)
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| EP2019134A1 (en) | 2007-07-26 | 2009-01-28 | Vision 7 GmbH | Gene therapy of chronic granulomatous disease |
| KR20120088542A (ko) | 2009-04-13 | 2012-08-08 | 아프세스 게엠베하 & 씨오. 카게 | 종양 치료를 위한 조작된 중간엽 줄기세포 및 이를 사용하는 방법 |
| BR112012013780B8 (pt) * | 2009-12-08 | 2021-07-27 | Univ Illinois | biorreator para modular linfócitos e suprimir células t autorreativas, sistema para inibição de um distúrbio autoimune, e, método ativar células t reguladoras |
| CN101974485A (zh) * | 2010-11-12 | 2011-02-16 | 苏州大学 | 具有最佳迁移能力的间充质干细胞的制备方法及其应用 |
| US9101597B2 (en) | 2013-03-14 | 2015-08-11 | The Administration Of The Tulane Educational Fund | Immunoprotective primary mesenchymal stem cells and methods |
| AR097570A1 (es) * | 2013-09-06 | 2016-03-23 | Consejo Nac De Investig Científicas Y Técnicas (Conicet) | Composiciones y métodos para incrementar la migración de células mesenquimales del estroma hacia tumores |
| 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 |
| WO2016146819A1 (en) * | 2015-03-18 | 2016-09-22 | Apceth Gmbh & Co. Kg | Hypoxia-induced expression of therapeutic proteins in mesenchymal stem cells |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1658853A1 (en) * | 2003-06-27 | 2006-05-24 | Renomedix Institute Inc. | Remedy for internal administration against cranial nerve diseases containing mesenchymal cells as the active ingredient |
| WO2008150368A1 (en) * | 2007-05-24 | 2008-12-11 | Apceth Gmbh & Co. Kg | Cd34 stem cell-related methods and compositions |
Non-Patent Citations (5)
| Title |
|---|
| Anonymous, "European Business Development Conference", (2013-09-23), URL: http://www.biodeutschland.org/tl_files/content/veranstaltungen/2013/BDC 2013/Presentationen/EBDC2013_apceth_Guenther.pdf, (2015-11-09) * |
| E. C. TSARK ET AL, THE JOURNAL OF IMMUNOLOGY, US, (2001-01-01), vol. 166, no. 1, doi:10.4049/jimmunol.166.1.170, ISSN 0022-1767, pages 170 - 181 * |
| GAO P ET AL, CANCER LETTERS, NEW YORK, NY, US, vol. 290, no. 2, doi:10.1016/J.CANLET.2009.08.031, ISSN 0304-3835, (2010-04-28), pages 157 - 166, (2009-09-27) * |
| HU Y L ET AL, "Mesenchymal stem cells: A promising targeted-delivery vehicle in cancer gene therapy", JOURNAL OF CONTROLLED RELEASE, ELSEVIER, AMSTERDAM, NL, vol. 147, no. 2, ISSN 0168-3659, (2010-10-15), pages 154 - 162, (2010-05-19) * |
| LI A ET AL, IMMUNOLOGY LETTERS, ELSEVIER BV, NL, vol. 98, no. 2, ISSN 0165-2478, (2005-05-15), pages 216 - 224, (2005-05-15) * |
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| EP3182984B1 (en) | 2019-10-30 |
| US11464806B2 (en) | 2022-10-11 |
| AU2015306231A1 (en) | 2017-02-23 |
| US20170239297A1 (en) | 2017-08-24 |
| CN106659742A (zh) | 2017-05-10 |
| CA2956987C (en) | 2023-03-21 |
| CA2956987A1 (en) | 2016-02-25 |
| WO2016026854A2 (en) | 2016-02-25 |
| EP3182984A2 (en) | 2017-06-28 |
| EP3656387A2 (en) | 2020-05-27 |
| EP3656387A3 (en) | 2020-07-01 |
| JP6712993B2 (ja) | 2020-06-24 |
| CN106659742B (zh) | 2021-09-03 |
| WO2016026854A3 (en) | 2016-04-14 |
| US20200268802A1 (en) | 2020-08-27 |
| JP2017525364A (ja) | 2017-09-07 |
| IL250388B (en) | 2021-02-28 |
| IL250388A0 (en) | 2017-03-30 |
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