RU2705244C2 - Композиции и способы лечения рака мозга - Google Patents
Композиции и способы лечения рака мозга Download PDFInfo
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| WO2011070440A2 (en) | 2009-12-10 | 2011-06-16 | Ottawa Hospital Research Institute | Oncolytic rhabdovirus |
| EP2718427B1 (en) | 2011-06-08 | 2017-01-11 | Children's Hospital of Eastern Ontario Research Institute Inc. | Compositions for glioblastoma treatment |
| EP3622965A1 (en) | 2013-02-21 | 2020-03-18 | Turnstone Limited Partnership | Vaccine composition |
| EP3624825A4 (en) * | 2017-05-19 | 2021-03-10 | Georgia State University Research Foundation, Inc. | RECOMBINANT ONCOLYTIC VIRUS |
| JP2020534007A (ja) | 2017-09-22 | 2020-11-26 | サントル ナショナル ドゥ ラ ルシェルシュ シアンティフィック | 変異型ウイルスタンパク質 |
| DE102018215551A1 (de) * | 2018-09-12 | 2020-03-12 | Virolutions Biotech Gmbh | Verfahren zur Herstellung eines antitumoralen Arenavirus sowie Arenavirusmutanten |
| CN112442114A (zh) * | 2019-08-29 | 2021-03-05 | 渥太华Hdl药物研发公司 | 一种多肽及其应用 |
| WO2022170219A1 (en) | 2021-02-05 | 2022-08-11 | Iovance Biotherapeutics, Inc. | Adjuvant therapy for cancer |
| US12440564B2 (en) | 2023-09-25 | 2025-10-14 | Kelonia Therapeutics, Inc. | Compositions for treating cancer |
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| RU2301260C2 (ru) * | 2000-09-22 | 2007-06-20 | Вирэкссис Корпорейшн | Вирусные векторы с зависимой от условий репликацией и их применение |
| CA2739963A1 (en) * | 2008-10-08 | 2010-04-15 | Tsanan Heimann | Lcmv-gp-vsv pseudotyped vectors and tumor infiltrating virus-producing cells for the therapy of tumors |
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| RU2301260C2 (ru) * | 2000-09-22 | 2007-06-20 | Вирэкссис Корпорейшн | Вирусные векторы с зависимой от условий репликацией и их применение |
| CA2739963A1 (en) * | 2008-10-08 | 2010-04-15 | Tsanan Heimann | Lcmv-gp-vsv pseudotyped vectors and tumor infiltrating virus-producing cells for the therapy of tumors |
Non-Patent Citations (7)
| Title |
|---|
| ALEXANDER MUIK et al., Pseudotyping Vesicular Stomatitis Virus with Lymphocytic Choriomeningitis Virus Glycoproteins Enhances Infectivity for Glioma Cells and Minimizes Neurotropism, JOURNAL OF VIROLOGY, June 2011, Vol. 85, No. 11, pp.5679-5684. * |
| GUIDO WOLLMANN et al., Oncolytic Virus Therapy of Glioblastoma Multiforme - Concepts;and Candidates, Cancer J. 2012, Vol.18, No.1, pp. 69-81. * |
| GUIDO WOLLMANN et al., Oncolytic Virus Therapy of Glioblastoma Multiforme - Concepts;and Candidates, Cancer J. 2012, Vol.18, No.1, pp. 69-81. ALEXANDER MUIK et al., Pseudotyping Vesicular Stomatitis Virus with Lymphocytic Choriomeningitis Virus Glycoproteins Enhances Infectivity for Glioma Cells and Minimizes Neurotropism, JOURNAL OF VIROLOGY, June 2011, Vol. 85, No. 11, pp.5679-5684. WINFRIED R. BEYER et al., Oncoretrovirus and Lentivirus Vectors Pseudotyped with Lymphocytic Choriomeningitis Virus Glycoprotein: Generation, Concentration, and Broad Host Range, JOURNAL OF VIROLOGY Feb. 2002, Vol. 76, No. 3, pp. 1488-1495. JAN BRUN et al., Identification of Genetically Modified Maraba Virus as an Oncolytic Rhabdovirus, Molecular Therapy Aug. 2010, Vol. 18, No.8, pp.1440-1449. * |
| JAN BRUN et al., Identification of Genetically Modified Maraba Virus as an Oncolytic Rhabdovirus, Molecular Therapy Aug. 2010, Vol. 18, No.8, pp.1440-1449. * |
| Maraba virus from Brazil, complete genome, GenBank: * |
| Maraba virus from Brazil, complete genome, GenBank: HQ6600766, 22.06.2011. * |
| WINFRIED R. BEYER et al., Oncoretrovirus and Lentivirus Vectors Pseudotyped with Lymphocytic Choriomeningitis Virus Glycoprotein: Generation, Concentration, and Broad Host Range, JOURNAL OF VIROLOGY Feb. 2002, Vol. 76, No. 3, pp. 1488-1495. * |
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| EP2931880B1 (en) | 2019-03-20 |
| AU2012396787B9 (en) | 2019-10-03 |
| MX366493B (es) | 2019-07-10 |
| JP6162818B2 (ja) | 2017-07-12 |
| IL239374A0 (en) | 2015-07-30 |
| RU2015128078A (ru) | 2019-03-27 |
| CA2894618A1 (en) | 2014-06-19 |
| MX2015007093A (es) | 2016-01-12 |
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