CA2982896A1 - Use of modified vaccinia ankara virus (mva) or mva with a deletion of virulence factor e8 as immunotherapeutic agent against solid tumors - Google Patents
Use of modified vaccinia ankara virus (mva) or mva with a deletion of virulence factor e8 as immunotherapeutic agent against solid tumorsInfo
- Publication number
- CA2982896A1 CA2982896A1 CA2982896A CA2982896A CA2982896A1 CA 2982896 A1 CA2982896 A1 CA 2982896A1 CA 2982896 A CA2982896 A CA 2982896A CA 2982896 A CA2982896 A CA 2982896A CA 2982896 A1 CA2982896 A1 CA 2982896A1
- Authority
- CA
- Canada
- Prior art keywords
- mva
- tumor
- cells
- mvaae3l
- immune
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6843736B2 (ja) * | 2014-07-16 | 2021-03-17 | トランジェーヌTransgene | 腫瘍溶解性ウイルスと免疫チェックポイントモジュレーターとの組合せ |
| WO2016144564A2 (en) | 2015-02-25 | 2016-09-15 | Memorial Sloan-Kettering Cancer Center | Use of inactivated nonreplicating modified vaccinia virus ankara (mva)as monoimmunotherapy or in combination with immune checkpoint blocking agents for solid tumors |
| EP3283088A4 (en) | 2015-04-17 | 2018-10-24 | Memorial Sloan-Kettering Cancer Center | Use of mva or mvadeltae3l as immunotherapeutic agents against solid tumors |
| FR3042121A1 (fr) * | 2015-10-08 | 2017-04-14 | Jean-Marc Limacher | Composition anti-tumorale |
| WO2017123675A1 (en) | 2016-01-11 | 2017-07-20 | Synlogic, Inc. | Microorganisms programmed to produce immune modulators and anti-cancer therapeutics in tumor cells |
| CA3015650A1 (en) | 2016-02-25 | 2017-08-31 | Memorial Sloan Kettering Cancer Center | Replication competent attenuated vaccinia viruses with deletion of thymidine kinase with and without the expression of human flt3l or gm-csf for cancer immunotherapy |
| EP3419662A4 (en) * | 2016-02-25 | 2019-09-18 | Memorial Sloan Kettering Cancer Center | HUMAN FLT3L EXPRESSIVE RECOMBINANT MVA OR MVADELE3L AND USE THEREOF AS IMMUNOTHERAPEUTICS AGAINST SOLID TUMORS |
| EP3621646A4 (en) | 2017-05-12 | 2021-06-02 | Memorial Sloan Kettering Cancer Center | USEFUL VACCINE VIRUS MUTANTS FOR ANTI-CANCER IMMUNOTHERAPY |
| AU2019262150A1 (en) * | 2018-05-02 | 2020-11-19 | Tonix Pharma Holdings Limited | Stem cells comprising synthetic chimeric vaccinia virus and methods of using them |
| BR112021004692A2 (pt) | 2018-09-15 | 2021-06-08 | Memorial Sloan Kettering Cancer Center | poxvírus recombinantes para imunoterapia de câncer |
| WO2020097424A1 (en) * | 2018-11-08 | 2020-05-14 | Synlogic Operating Company, Inc. | Combination therapies of microorganisms and immune modulators for use in treating cancer |
| TWI852977B (zh) | 2019-01-10 | 2024-08-21 | 美商健生生物科技公司 | 前列腺新抗原及其用途 |
| PH12022551208A1 (en) | 2019-11-18 | 2023-04-24 | Janssen Biotech Inc | Vaccines based on mutant calr and jak2 and their uses |
| WO2022009052A2 (en) | 2020-07-06 | 2022-01-13 | Janssen Biotech, Inc. | Prostate neoantigens and their uses |
| CN118086493B (zh) * | 2024-01-17 | 2025-08-26 | 中山大学附属第六医院 | 一种肿瘤治疗及疗效预测靶点及其应用 |
Family Cites Families (126)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5833975A (en) | 1989-03-08 | 1998-11-10 | Virogenetics Corporation | Canarypox virus expressing cytokine and/or tumor-associated antigen DNA sequence |
| JP3602530B2 (ja) | 1991-03-07 | 2004-12-15 | ヴァイロジェネティクス コーポレイション | 遺伝子操作したワクチン菌株 |
| DE69534289T2 (de) | 1994-04-29 | 2006-04-27 | Baxter Healthcare S.A. | Rekombinante Pockenviren mit fremden Polynukleotiden in wichtigen Regionen |
| US6093700A (en) | 1995-05-11 | 2000-07-25 | Thomas Jefferson University | Method of inducing an immune response using vaccinia virus recombinants encoding GM-CSF |
| EP1016418B1 (en) | 1994-10-03 | 2009-12-30 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Host cell comprising a recombinant virus expressing an antigen and a recombinant virus expressing an immunostimulatory molecule |
| US6004777A (en) | 1997-03-12 | 1999-12-21 | Virogenetics Corporation | Vectors having enhanced expression, and methods of making and uses thereof |
| US20030044384A1 (en) | 1997-10-09 | 2003-03-06 | Pro-Virus, Inc. | Treatment of neoplasms with viruses |
| GB9825303D0 (en) * | 1998-11-18 | 1999-01-13 | Oxford Biomedica Ltd | Vector |
| WO2000073487A1 (en) | 1999-05-27 | 2000-12-07 | Arizona Board Of Regents | Novel viral vectors having enhanced effectiveness with dramatically reduced virulence |
| CA2375189C (en) | 1999-05-28 | 2010-02-09 | The Government Of The United States Of America | A combined growth factor-deleted and thymidine kinase-deleted vaccinia virus vector |
| EP1227828A1 (en) | 1999-11-12 | 2002-08-07 | Oncolytics Biotech, Inc. | Viruses for the treatment of cellular proliferative disorders |
| US7306902B2 (en) | 2002-06-28 | 2007-12-11 | Oncolyties Biotech Inc. | Oncolytic viruses as phenotyping agents for neoplasms |
| BR0115127A (pt) | 2000-11-20 | 2004-02-17 | Oncolytics Biotech Inc | Método de fornecer um vìrus a um tumor sólido para reduzir crescimento do tumor |
| NZ524661A (en) | 2000-11-23 | 2005-03-24 | Bavarian Nordic As | Modified vaccinia ankara virus variant |
| US6750043B2 (en) | 2001-04-19 | 2004-06-15 | Arizona Board Of Regents | Viral vectors having reduced virulence |
| US6372455B1 (en) | 2001-04-19 | 2002-04-16 | Arizona Board Of Regents | Recombinant vaccinia viral vectors |
| US20040091995A1 (en) | 2001-06-15 | 2004-05-13 | Jeffrey Schlom | Recombinant non-replicating virus expressing gm-csf and uses thereof to enhance immune responses |
| US20030113919A1 (en) | 2001-08-17 | 2003-06-19 | Aventis Pasteur, Ltd. | Immunogenic targets for melanoma |
| DE10144664B4 (de) * | 2001-09-11 | 2005-06-09 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Vacciniavirus MVA-E3L-Knock-Out-Mutanten und Verwendung hiervon |
| US7001718B2 (en) | 2001-12-20 | 2006-02-21 | Massachusetts Institute Of Technology | Method of inhibiting pathogenicity of infectious agents |
| NZ536592A (en) | 2002-04-19 | 2007-01-26 | Bavarian Nordic As | Modified vaccinia virus ankara for the vaccination of neonates |
| US20070178065A1 (en) | 2002-05-03 | 2007-08-02 | Lattime Edmund C | Neutralizing factors as vaccine adjuvants |
| DE10221411B4 (de) | 2002-05-14 | 2004-07-08 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Rekombinantes Fowlpox-Virus |
| EP1407033B1 (en) | 2002-05-16 | 2006-01-11 | Bavarian Nordic A/S | Intergenic regions as insertion sites in the genome of modified vaccinia virus ankara (mva) |
| WO2004042001A2 (en) | 2002-05-17 | 2004-05-21 | Emory University | Virus-like particles, methods of preparation, and immonogenic compositions |
| JP2004031674A (ja) | 2002-06-26 | 2004-01-29 | Disco Abrasive Syst Ltd | コンタミネーション除去装置 |
| WO2004009763A2 (en) | 2002-07-24 | 2004-01-29 | Arizona Board Of Regents | Use of vaccinia virus deleted for the e3l gene as a vaccine vector |
| AU2003267361A1 (en) | 2002-09-12 | 2004-04-30 | Gsf-Forschungszentrum Fur Umwelt Und Gesundheit Gmbh | Orthopoxvirus antigens and use thereof |
| EP1575611A4 (en) | 2002-12-23 | 2007-10-03 | Hope City | MODIFIED P53-EXPRESSING VACCINIAANKARA IN CANCER IMMUNOTHERAPY |
| WO2004087047A2 (en) | 2003-02-07 | 2004-10-14 | Arizona Board Of Regents | Mutants of replication competent vaccinia virus |
| MXPA05013879A (es) | 2003-06-18 | 2006-06-27 | Genelux Corp | Virus de la vaccinia recombinantes modificados y otros microorganismos, y usos de los mismos. |
| WO2005007824A2 (en) | 2003-07-08 | 2005-01-27 | Arizona Board Of Regents | Mutants of vaccinia virus as oncolytic agents |
| CA2436196A1 (en) | 2003-07-25 | 2005-01-25 | Oncolytics Biotech Inc. | Oncolytic virus for purging cellular compositions of cells of lymphoid malignancies |
| CA2435967A1 (en) | 2003-07-25 | 2005-01-25 | Oncolytics Biotech, Inc. | Reovirus for the treatment of lymphoid malignancies |
| EP1678292A4 (en) | 2003-09-18 | 2008-05-07 | Univ Emory | IMPROVED MVA VACCINES |
| EP1518932A1 (en) * | 2003-09-29 | 2005-03-30 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Modified vaccinia virus Ankara (MVA) mutant and use thereof |
| JP4995575B2 (ja) * | 2003-11-12 | 2012-08-08 | アメリカ合衆国 | 乳癌を処置および予防するためのシステム |
| EP2338524B1 (en) | 2004-08-12 | 2013-05-22 | Cedars-Sinai Medical Center | Combined gene therapy for the treatment of macroscopic gliomas |
| EP1683870A1 (en) | 2005-01-24 | 2006-07-26 | GSF-Forschungszentrum für Umwelt und Gesundheit GmbH | Vaccines based on the use of MVA |
| WO2006120474A2 (en) | 2005-05-13 | 2006-11-16 | Oxxon Therapeutics Ltd | Compositions for inducing an immune response against tumor antigens |
| US10543277B2 (en) | 2005-05-30 | 2020-01-28 | Arjuna Natural Private Limited | Formulation of curcumin with enhanced bioavailability of curcumin and method of preparation and treatment thereof |
| ES2281252B1 (es) | 2005-07-27 | 2009-02-16 | Consejo Superior De Investigaciones Cientificas | Vectores recombinantes basados en el virus modificado de ankara (mva) como vacunas preventivas y terapeuticas contra el sida. |
| US8980246B2 (en) | 2005-09-07 | 2015-03-17 | Sillajen Biotherapeutics, Inc. | Oncolytic vaccinia virus cancer therapy |
| US20070077231A1 (en) | 2005-09-30 | 2007-04-05 | Contag Christopher H | Immune effector cells pre-infected with oncolytic virus |
| CA2642994C (en) | 2006-02-24 | 2015-09-01 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Immunogenic page-4 peptides and methods of use |
| US7919079B2 (en) | 2006-03-31 | 2011-04-05 | Biosante Pharmaceuticals, Inc. | Cancer immunotherapy compositions and methods of use |
| KR100788930B1 (ko) | 2006-04-18 | 2007-12-27 | 포항공과대학교 산학협력단 | 항암 조성물 |
| CA2665068C (en) | 2006-10-06 | 2016-01-05 | Bn Immunotherapeutics Inc. | Methods for treating cancer with mva |
| US8052968B2 (en) | 2006-10-16 | 2011-11-08 | Genelux Corporation | Modified vaccinia virus strains for use in diagnostic and therapeutic methods |
| US20100316609A1 (en) | 2006-10-18 | 2010-12-16 | University Of Rochester | Conditionally Replicating Viruses for Cancer Therapy |
| AU2008209759B2 (en) * | 2007-01-30 | 2013-03-21 | Transgene S.A. | Papillomavirus E2 polypeptide used for vaccination |
| KR20080084528A (ko) | 2007-03-15 | 2008-09-19 | 제네렉스 바이오테라퓨틱스 인크. | 종양살상형 백시니아 바이러스 암 치료 |
| JP5213075B2 (ja) | 2007-06-15 | 2013-06-19 | ジェネラックス・コーポレイション | 腫瘍の画像化および/または処置のための微生物 |
| JP2010533718A (ja) | 2007-07-18 | 2010-10-28 | ジェネラックス・コーポレイション | 腫瘍溶解性ウイルス治療に付随する副作用の処置もしくは改善用医薬の製造における化学治療剤の使用 |
| NZ584042A (en) | 2007-10-18 | 2012-09-28 | Bn Immunotherapeutics Inc | Use of mva to treat prostate cancer |
| WO2009052617A1 (en) | 2007-10-22 | 2009-04-30 | Oncolytics Biotech Inc. | Treatment regime for proliferative disorders |
| PL2212345T3 (pl) | 2007-11-19 | 2016-07-29 | Transgene Sa | Onkolityczne wektory pokswirusowe |
| RU2508401C2 (ru) | 2007-11-19 | 2014-02-27 | Трансжене С.А. | Поксвирусные онколитические векторы |
| US20120052003A9 (en) | 2008-05-16 | 2012-03-01 | Szalay Aladar A | Microorganisms for preventing and treating neoplasms accompanying cellular therapy |
| US20110142874A1 (en) | 2008-06-09 | 2011-06-16 | Arizona Board Of Regents | Compositions, Methods, and Kits for Eliciting an Immune Response |
| US10603351B2 (en) | 2008-08-21 | 2020-03-31 | Turnstone Limited Partnership | Engineered synergistic oncolytic viral symbiosis |
| CA2760315C (en) | 2009-04-30 | 2019-05-28 | Centre Hospitalier Universitaire Vaudois Lausanne (Chuv) | Modified immunization vectors |
| CA2709292A1 (en) | 2009-07-10 | 2011-01-10 | The Governors Of The University Of Alberta | Oncolytic viruses and methods for treating neoplastic disorders |
| JP5879266B2 (ja) | 2009-09-14 | 2016-03-08 | シラジェン バイオセラピューティクス インコーポレイテッド | 腫瘍崩壊性ワクシニアウイルスの併用癌療法 |
| GB201006405D0 (en) | 2010-04-16 | 2010-06-02 | Isis Innovation | Poxvirus expression system |
| WO2011156470A1 (en) | 2010-06-08 | 2011-12-15 | Arizona Board of Regents, a body corporate acting for and on behalf of Arizona State University | A method for inserting genetic material into genomic dna |
| US20130230884A1 (en) | 2010-07-16 | 2013-09-05 | John Chaput | Methods to Identify Synthetic and Natural RNA Elements that Enhance Protein Translation |
| EP2618840A2 (en) | 2010-09-23 | 2013-07-31 | Baxter International Inc. | Recombinant viral vectors and methods for inducing an immune response to yellow fever virus |
| CA2824277C (en) | 2011-01-04 | 2021-08-31 | Jennerex, Inc. | Generation of antibodies to tumor antigens and generation of tumor specific complement dependent cytotoxicity by administration of oncolytic vaccinia virus |
| KR101937279B1 (ko) * | 2011-03-21 | 2019-01-10 | 비보룩스 아베 | 고형 종양의 치료 방법 |
| ES2733211T3 (es) | 2011-04-15 | 2019-11-28 | Genelux Corp | Cepas clonales de virus vaccinia atenuados y métodos de uso de las mismas |
| WO2012177624A2 (en) | 2011-06-21 | 2012-12-27 | The Johns Hopkins University | Focused radiation for augmenting immune-based therapies against neoplasms |
| FI20115914L (fi) | 2011-09-16 | 2013-03-17 | Oncos Therapeutics Ltd | Muunnettu onkolyyttinen virus |
| WO2013052915A2 (en) | 2011-10-05 | 2013-04-11 | Genelux Corporation | Method for detecting replication or colonization of a biological therapeutic |
| WO2013063348A1 (en) | 2011-10-28 | 2013-05-02 | Arizona Board Of Regents, A Body Corporate Of The State Of Arizona, Acting For And On Behalf Of Arizona State University | Genetic element that enhances protein translation |
| WO2013138522A2 (en) | 2012-03-16 | 2013-09-19 | Genelux Corporation | Methods for assessing effectiveness and monitoring oncolytic virus treatment |
| US20140086976A1 (en) * | 2012-08-20 | 2014-03-27 | Aladar A. Szalay | Compositions containing protein polymers and vaccinia virus, and methods of use thereof |
| CN114984062A (zh) | 2012-08-30 | 2022-09-02 | 安姆根有限公司 | 使用单纯疱疹病毒和免疫检查点抑制剂治疗黑色素瘤的方法 |
| EP3639851A1 (en) | 2012-09-04 | 2020-04-22 | Bavarian Nordic A/S | Methods and compositions for enhancing vaccine immune responses |
| US20150250837A1 (en) | 2012-09-20 | 2015-09-10 | Morningside Technology Ventures Ltd. | Oncolytic virus encoding pd-1 binding agents and uses of the same |
| TWI690322B (zh) | 2012-10-02 | 2020-04-11 | 法商傳斯堅公司 | 含病毒的調配物及其使用 |
| JP2016502507A (ja) | 2012-10-19 | 2016-01-28 | バヴァリアン・ノルディック・インコーポレイテッド | 癌治療のための組成物および方法 |
| US20180200320A1 (en) | 2012-11-21 | 2018-07-19 | Aviratek Biomedical Solutions, Llc | Method and compositions for the use of botanical extracts in the treatment of viral infections, cancer, pain, itch, and inflammation |
| US20140193859A1 (en) | 2013-01-08 | 2014-07-10 | Bertram Jacobs | Temperature-dependent insertion of genetic material into genomic DNA |
| US20140271549A1 (en) | 2013-03-15 | 2014-09-18 | Aladar A. Szalay | Use of Antibiotics to Enhance Treatment With Therapeutic Viruses |
| KR102182485B1 (ko) | 2013-05-28 | 2020-11-25 | 카오슝 메디칼 유니버시티 | 단백질 약물의 불활성화를 위한 항체 로커 |
| GB201310917D0 (en) | 2013-06-19 | 2013-07-31 | Cancer Res Inst Royal | Vaccinia virus for gene-directed enzyme prodrug therapy |
| PE20160673A1 (es) | 2013-08-22 | 2016-07-21 | Univ Of Pittsburgh - Of The Commonwealth System Of Higher Education | Terapias inmuno-oncoliticas |
| WO2015066715A1 (en) | 2013-11-04 | 2015-05-07 | Viracell Advanced Products, Llc | Virus-like particles and methods related thereto |
| RU2714142C2 (ru) | 2013-11-05 | 2020-02-12 | Бавариан Нордик А/С | Комбинированное лекарственное средство для лечения рака с использованием поксвируса, экспрессирующего опухолевый антиген, и антагониста и/или агониста ингибитора имунной контрольной точки |
| CN106061488B (zh) | 2013-12-02 | 2021-04-09 | 菲奥医药公司 | 癌症的免疫治疗 |
| NZ721908A (en) | 2013-12-20 | 2022-12-23 | Massachusetts Gen Hospital | Combination therapy with neoantigen vaccine |
| US20170106065A1 (en) | 2013-12-31 | 2017-04-20 | Bavarian Nordic A/S | Combination Therapy for Treating Cancer with a Poxvirus Expressing a Tumor Antigen and an Antagonist of TIM-3 |
| US20170021009A1 (en) | 2014-03-10 | 2017-01-26 | Arizona Board Of Regents On Behalf Of Arizona State | Heat Inactivated Poxvirus Improves Vaccination Results |
| WO2015138741A1 (en) | 2014-03-12 | 2015-09-17 | Cars-N-Kids Llc | Systems and methods for determining if a child safety seat is in a moving vehicle |
| GB201405834D0 (en) | 2014-04-01 | 2014-05-14 | Univ London Queen Mary | Oncolytic virus |
| AU2015259510B2 (en) | 2014-05-13 | 2020-10-01 | Bavarian Nordic A/S | Combination therapy for treating cancer with a recombinant poxvirus expressing a tumor antigen and an immune checkpoint molecule antagonist or agonist |
| CA3190510A1 (en) | 2014-07-16 | 2016-01-21 | Transgene Sa | Oncolytic virus for expression of immune checkpoint modulators |
| JP6843736B2 (ja) | 2014-07-16 | 2021-03-17 | トランジェーヌTransgene | 腫瘍溶解性ウイルスと免疫チェックポイントモジュレーターとの組合せ |
| WO2016046357A1 (en) | 2014-09-26 | 2016-03-31 | Bavarian Nordic A/S | Methods and compositions for intra-nasal immunization with recombinant mva encoding flagellin |
| KR101645642B1 (ko) | 2014-10-16 | 2016-08-11 | 대한민국 | Kvac103 유래의 재조합 백시니아 바이러스 |
| US20180028626A1 (en) | 2015-02-13 | 2018-02-01 | Transgene Sa | Immunotherapeutic vaccine and antibody combination therapy |
| WO2016144564A2 (en) | 2015-02-25 | 2016-09-15 | Memorial Sloan-Kettering Cancer Center | Use of inactivated nonreplicating modified vaccinia virus ankara (mva)as monoimmunotherapy or in combination with immune checkpoint blocking agents for solid tumors |
| EP3283088A4 (en) * | 2015-04-17 | 2018-10-24 | Memorial Sloan-Kettering Cancer Center | Use of mva or mvadeltae3l as immunotherapeutic agents against solid tumors |
| EP3307330B1 (en) | 2015-06-15 | 2021-03-10 | New York University | Method of treatment using oncolytic viruses |
| EP3310383B1 (en) | 2015-06-19 | 2020-02-19 | Sillajen, Inc. | Compositions and methods for viral embolization |
| CN105039269A (zh) | 2015-07-24 | 2015-11-11 | 北京鼎成肽源生物技术有限公司 | 一种用于治疗非小细胞肺癌的新型病毒疫苗及其制备方法 |
| US10550164B2 (en) | 2015-08-03 | 2020-02-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Brachyury deletion mutants, non-yeast vectors encoding Brachyury deletion mutants, and their use |
| AU2016320355B2 (en) | 2015-09-08 | 2020-10-08 | Sillajen, Inc. | Modified oncolytic vaccinia viruses expressing a cytokine and a car- boxylesterase and methods of use thereof |
| JP2018526428A (ja) | 2015-09-09 | 2018-09-13 | ティーブイエーエックス バイオメディカル アイ,リミティド ライアビリティ カンパニー | 養子t細胞療法と腫瘍溶解性ウイルス補助療法とを組み合わせる方法 |
| JP7171433B2 (ja) | 2015-10-30 | 2022-11-15 | ザ ユナイテッド ステイツ オブ アメリカ, アズ リプレゼンテッド バイ ザ セクレタリー, デパートメント オブ ヘルス アンド ヒューマン サービシーズ | Her-2発現固形腫瘍の処置のための組成物および方法 |
| KR20180108590A (ko) | 2015-12-17 | 2018-10-04 | 싸이오서스 테라퓨틱스 엘티디. | 항-tcr-복합체 항체 또는 단편을 암호화하는 바이러스 |
| HUE059343T2 (hu) | 2016-01-29 | 2022-11-28 | Bavarian Nordic As | Rekombináns, módosított Ankara Vaccinia vírus (MVA) és ló encephalitis vírus oltóanyag |
| EP3419662A4 (en) * | 2016-02-25 | 2019-09-18 | Memorial Sloan Kettering Cancer Center | HUMAN FLT3L EXPRESSIVE RECOMBINANT MVA OR MVADELE3L AND USE THEREOF AS IMMUNOTHERAPEUTICS AGAINST SOLID TUMORS |
| CA3015650A1 (en) | 2016-02-25 | 2017-08-31 | Memorial Sloan Kettering Cancer Center | Replication competent attenuated vaccinia viruses with deletion of thymidine kinase with and without the expression of human flt3l or gm-csf for cancer immunotherapy |
| EP3426271B1 (en) | 2016-03-10 | 2025-08-27 | CG Oncology, Inc. | Methods of treating solid tumors by combination therapy |
| WO2017205674A1 (en) | 2016-05-25 | 2017-11-30 | Arizona Board Of Regents On Behalf Of Arizona State University | Oncolytic vaccinia virus mutants and using same for cancer treatment |
| US10888594B2 (en) | 2016-05-30 | 2021-01-12 | National University Corporation Tottori University | Genetically engineered vaccinia viruses |
| EP3488005A4 (en) | 2016-07-19 | 2020-07-29 | University of Pittsburgh- Of the Commonwealth System of Higher Education | TARGETING ONCOLYTIC VIRUSES STAT3 |
| GB201612520D0 (en) | 2016-07-19 | 2016-08-31 | F-Star Beta Ltd | Binding molecules |
| WO2018016917A1 (ko) | 2016-07-21 | 2018-01-25 | 코오롱생명과학 주식회사 | 재조합 백시니아 바이러스 및 이의 용도 |
| EP3497209A4 (en) | 2016-08-09 | 2020-07-29 | City of Hope | CHEMERICAL POXVIRUS COMPOSITIONS AND THEIR USES |
| TW201825674A (zh) | 2016-09-09 | 2018-07-16 | 美商艾斯合顧問有限公司 | 表現雙特異性接合分子的溶瘤病毒 |
| JP2019528753A (ja) | 2016-09-21 | 2019-10-17 | スティーブン エイチ. ソーン, | 高移動度グループboxi突然変異体 |
| US20200046784A1 (en) | 2016-09-30 | 2020-02-13 | University Health Network | Recombinant oncolytic viruses for cancer therapy |
| BR112021004692A2 (pt) | 2018-09-15 | 2021-06-08 | Memorial Sloan Kettering Cancer Center | poxvírus recombinantes para imunoterapia de câncer |
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- 2016-04-18 CN CN202211127994.4A patent/CN116173193A/zh active Pending
- 2016-04-18 KR KR1020177032858A patent/KR20180006916A/ko not_active Ceased
- 2016-04-18 US US15/565,609 patent/US10548930B2/en active Active
- 2016-04-18 AU AU2016249521A patent/AU2016249521B2/en active Active
- 2016-04-18 JP JP2017554498A patent/JP6936153B2/ja active Active
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2020
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| CN107847534A (zh) | 2018-03-27 |
| EP3283088A1 (en) | 2018-02-21 |
| HK1252730A1 (zh) | 2019-05-31 |
| US10548930B2 (en) | 2020-02-04 |
| US20180078591A1 (en) | 2018-03-22 |
| JP6936153B2 (ja) | 2021-09-15 |
| AU2016249521A1 (en) | 2017-11-02 |
| KR20180006916A (ko) | 2018-01-19 |
| AU2021261933A1 (en) | 2021-12-16 |
| BR112017022134A2 (pt) | 2018-07-31 |
| US20200222479A1 (en) | 2020-07-16 |
| CN116173193A (zh) | 2023-05-30 |
| EP3283088A4 (en) | 2018-10-24 |
| JP2021191765A (ja) | 2021-12-16 |
| US20220211785A1 (en) | 2022-07-07 |
| AU2021261933B2 (en) | 2025-04-03 |
| US11253560B2 (en) | 2022-02-22 |
| CN107847534B (zh) | 2022-10-04 |
| JP2018513165A (ja) | 2018-05-24 |
| JP2023129416A (ja) | 2023-09-14 |
| AU2016249521B2 (en) | 2021-08-19 |
| JP7366091B2 (ja) | 2023-10-20 |
| US12397029B2 (en) | 2025-08-26 |
| WO2016168862A1 (en) | 2016-10-20 |
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