JP5727458B2 - 改変間葉系幹細胞及びそれを使用した腫瘍の治療方法 - Google Patents
改変間葉系幹細胞及びそれを使用した腫瘍の治療方法 Download PDFInfo
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| US20140369979A1 (en) * | 2012-02-01 | 2014-12-18 | Postech Academy-Industry Foundation | Vector simultaneously expressing dodecameric trail and hsv-tk suicide genes, and anticancer stem cell therapeutic agent using same |
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| US10472647B2 (en) | 2012-12-21 | 2019-11-12 | The Administrators Of The Tulane Educational Fund | Primary mesenchymal stem cells as a vaccine platform |
| WO2015100268A1 (en) * | 2013-12-23 | 2015-07-02 | The Regents Of The University Of California | Mesenchymal stem cells for targeted cancer therapy |
| JP2017506884A (ja) * | 2014-01-17 | 2017-03-16 | ウェイク・フォレスト・ユニヴァーシティ・ヘルス・サイエンシズ | 活性薬の送達を増強するための方法 |
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| RU2716821C2 (ru) * | 2014-10-24 | 2020-03-17 | Калиди Биотерапьютикс, Инк. | Комбинированный иммунотерапевтический подход к лечению рака |
| CN104622903B (zh) * | 2015-01-20 | 2018-10-09 | 奥思达干细胞有限公司 | 抗恶性黑色素瘤的干细胞制剂及其制备方法 |
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| US10618944B2 (en) | 2015-02-27 | 2020-04-14 | Saint Louis University | Tumor suppressor SALL1 as a therapeutic agent for treating cancer |
| WO2016146819A1 (en) * | 2015-03-18 | 2016-09-22 | Apceth Gmbh & Co. Kg | Hypoxia-induced expression of therapeutic proteins in mesenchymal stem cells |
| EP3319631A4 (en) | 2015-07-08 | 2019-01-09 | American Gene Technologies International Inc. | HIV PREMUNICATION AND IMMUNOTHERAPY |
| EA201800148A1 (ru) | 2015-08-11 | 2019-01-31 | Калиди Биотерапьютикс, Инк. | Оспенная вакцина для лечения рака |
| WO2017036925A1 (en) * | 2015-08-28 | 2017-03-09 | Apceth Gmbh & Co. Kg | Mesenchymal stem cells for the treatment of metastatic liver disease |
| CA3011529A1 (en) | 2016-01-15 | 2017-07-20 | American Gene Technologies International Inc. | Methods and compositions for the activation of gamma-delta t-cells |
| US10137144B2 (en) | 2016-01-15 | 2018-11-27 | American Gene Technologies International Inc. | Methods and compositions for the activation of gamma-delta T-cells |
| US10888613B2 (en) | 2016-02-08 | 2021-01-12 | American Gene Technologies International Inc. | Method of producing cells resistant to HIV infection |
| ES2911448T3 (es) | 2016-03-09 | 2022-05-19 | American Gene Tech Int Inc | Vectores combinados y métodos para el tratamiento del cáncer |
| CN109561691A (zh) * | 2016-06-07 | 2019-04-02 | 太平洋心肺血研究所 | 用于治疗癌症的组合物和方法 |
| EP3468617A4 (en) | 2016-06-08 | 2020-01-22 | American Gene Technologies International Inc. | INTEGRATED VIRAL ADMINISTRATION SYSTEM AND RELATED METHODS |
| IL300730A (en) | 2016-07-08 | 2023-04-01 | American Gene Tech Int Inc | Pre-HIV vaccine and immunotherapy |
| JP7176756B2 (ja) | 2016-07-21 | 2022-11-22 | アメリカン ジーン テクノロジーズ インターナショナル インコーポレイテッド | パーキンソン病を処置するためのウイルスベクター |
| JP2019535691A (ja) | 2016-11-03 | 2019-12-12 | エグゾステム バイオテック リミテッド | 間葉系幹細胞集団、それらの生成物およびそれらの使用 |
| US11820999B2 (en) | 2017-04-03 | 2023-11-21 | American Gene Technologies International Inc. | Compositions and methods for treating phenylketonuria |
| SG10202111394XA (en) | 2017-04-13 | 2021-12-30 | Senti Biosciences Inc | Combinatorial cancer immunotherapy |
| WO2019195142A1 (en) | 2018-04-03 | 2019-10-10 | The Board Of Trustees Of The Leland Stanford Junior University | Mesenchymal stem cells comprising a chimeric antigen receptor (car) for treating inflammatory and autoimmune diseases |
| US11505782B2 (en) | 2018-06-04 | 2022-11-22 | Calidi Biotherapeutics, Inc. | Cell-based vehicles for potentiation of viral therapy |
| CA3103423A1 (en) * | 2018-06-14 | 2019-12-19 | Loma Linda University | Engineered hematopoietic stem cells for the treatment of acute myeloid leukemia |
| US11419898B2 (en) | 2018-10-17 | 2022-08-23 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
| AU2019359890B2 (en) | 2018-10-17 | 2024-10-24 | Senti Biosciences, Inc. | Combinatorial cancer immunotherapy |
| WO2020097049A1 (en) * | 2018-11-05 | 2020-05-14 | American Gene Technologies International Inc. | Vector system for expressing regulatory rna |
| AU2019377141B2 (en) | 2018-11-06 | 2024-06-06 | Calidi Biotherapeutics (Nevada), Inc. | Enhanced systems for cell-mediated oncolytic viral therapy |
| US20220241337A1 (en) * | 2019-02-22 | 2022-08-04 | The Trustees Of Columbia University In The City Of Newyork | Preparing tissues for delivery of therapeutic and diagnostic agents and delivering the agents |
| SG10201902002SA (en) * | 2019-03-06 | 2020-10-29 | Nat Univ Singapore | Non-viral modification of mesenchymal stem cells |
| EP4017512B1 (en) * | 2019-08-23 | 2025-04-02 | Orbsen Therapeutics Limited | Compositions for monocyte and macrophage polarization and methods of use |
| EP3995130A1 (en) | 2020-11-06 | 2022-05-11 | JunctuCell Biomed Manufacturing GmbH | A composition comprising extra-cellular vesicles from mesenchymal stem cells and alpha-1 antitrypsin for the treatment of viral infections |
| AU2021375735A1 (en) | 2020-11-06 | 2023-06-08 | Aatec Medical Gmbh | A composition comprising extra-cellular vesicles from mesenchymal stem cells and alpha-1 antitrypsin for the treatment of viral infections |
Family Cites Families (9)
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|---|---|---|---|---|
| US6265564B1 (en) * | 1996-08-02 | 2001-07-24 | Regeneron Pharmaceuticals, Inc. | Expressed ligand-vascular intercellular signalling molecule |
| US7098185B2 (en) * | 1998-05-18 | 2006-08-29 | University College London | Polypeptide hormone phosphatonin |
| WO2001091802A1 (en) * | 2000-05-30 | 2001-12-06 | Baylor College Of Medicine | Chimeric viral vectors for gene therapy |
| WO2002069953A1 (en) * | 2001-03-01 | 2002-09-12 | The Board Of Regents Of The University Of Texas System | Methods of treating lung inflammation |
| US20030165579A1 (en) * | 2002-02-27 | 2003-09-04 | Chih-Hui Lin | Euphorbia antiquorum extract, a pharmaceutical composition containing the same and methods for treatment of cancers |
| ATE386748T1 (de) * | 2003-12-19 | 2008-03-15 | Charite Universitaetsmedizin | Verwendung von liganden von cd52 antigen zur behandlung von soliden tumoren und von knochenkrebserkrankungen |
| JP2006194752A (ja) * | 2005-01-14 | 2006-07-27 | Sumitomo Metal Mining Co Ltd | X線回折測定における試料固定方法および試料固定具 |
| KR101022401B1 (ko) * | 2005-09-29 | 2011-03-15 | 아주대학교산학협력단 | 자살유전자를 발현하는 중간엽 줄기세포를 포함하는 암치료용 조성물 |
| BRPI0811906A2 (pt) * | 2007-05-24 | 2014-11-18 | Apceth Gmbh & Co Kg | Composições e métodos relacionados a célula-tronco cd34 |
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| CN102695517A (zh) | 2012-09-26 |
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| SG175127A1 (en) | 2011-11-28 |
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| AU2010237130B2 (en) | 2015-01-29 |
| EP2419113A1 (en) | 2012-02-22 |
| US20120087901A1 (en) | 2012-04-12 |
| CN102695517B (zh) | 2015-01-28 |
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