JP5985397B2 - 組換えリステリア株およびそれを含む免疫原性組成物 - Google Patents
組換えリステリア株およびそれを含む免疫原性組成物 Download PDFInfo
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- JP5985397B2 JP5985397B2 JP2012539021A JP2012539021A JP5985397B2 JP 5985397 B2 JP5985397 B2 JP 5985397B2 JP 2012539021 A JP2012539021 A JP 2012539021A JP 2012539021 A JP2012539021 A JP 2012539021A JP 5985397 B2 JP5985397 B2 JP 5985397B2
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| US9650639B2 (en) | 2008-05-19 | 2017-05-16 | Advaxis, Inc. | Dual delivery system for heterologous antigens |
| US20110129499A1 (en) | 2008-05-19 | 2011-06-02 | Paulo Maciag | Dual delivery system for heterologous antigens |
| JP5985397B2 (ja) | 2009-11-11 | 2016-09-06 | アドバクシス インコーポレイテッド | 組換えリステリア株およびそれを含む免疫原性組成物 |
| US10016617B2 (en) | 2009-11-11 | 2018-07-10 | The Trustees Of The University Of Pennsylvania | Combination immuno therapy and radiotherapy for the treatment of Her-2-positive cancers |
| WO2012138377A2 (en) | 2010-10-01 | 2012-10-11 | Trustees Of The University Of Pennsylvania | The use of listeria vaccine vectors to reverse vaccine unresponsiveness in parasitically infected individuals |
| ES2614880T3 (es) * | 2010-10-19 | 2017-06-02 | Merial, Inc. | Vacuna de ADN de HER2 como tratamiento auxiliar para cánceres en animales de compañía |
| CA2829960A1 (en) | 2011-03-11 | 2012-09-20 | John Rothman | Listeria-based adjuvants |
| WO2013110030A2 (en) | 2012-01-19 | 2013-07-25 | Duke University | Vaccines against antigens involved in therapy resistance and methods of using same |
| WO2013138337A1 (en) * | 2012-03-12 | 2013-09-19 | Advaxis | Suppressor cell function inhibition following listeria vaccine treatment |
| JP2017511796A (ja) | 2014-02-18 | 2017-04-27 | アドバクシス， インコーポレイテッド | 多標的免疫療法を目的とするバイオマーカー |
| CN103897067B (zh) * | 2014-04-16 | 2016-04-13 | 中国医学科学院基础医学研究所 | 一种治疗肿瘤的重组多肽 |
| EP3134510B1 (en) | 2014-04-24 | 2023-11-01 | Advaxis, Inc. | Recombinant listeria vaccine strains and methods of producing the same |
| SG11201609135VA (en) * | 2014-05-02 | 2016-11-29 | Univ Pennsylvania | Combination immuno therapy and radiotherapy for the treatment of her-2-positive cancers |
| CA2954279C (en) | 2014-07-07 | 2023-11-14 | Duke University | Vaccines against an oncogenic isoform of esr1 and methods of using the same |
| EP3166646A4 (en) * | 2014-07-07 | 2018-03-07 | Duke University | Vaccines against an oncogenic isoform of her2 (erbb2) and methods of using the same |
| WO2016011320A1 (en) * | 2014-07-18 | 2016-01-21 | Advaxis, Inc. | Bivalent listeria-based delivery system of heterologous antigens |
| CN107429289A (zh) * | 2014-10-14 | 2017-12-01 | 宾夕法尼亚大学理事会 | 用于癌症治疗的联合疗法 |
| MA41644A (fr) | 2015-03-03 | 2018-01-09 | Advaxis Inc | Compositions à base de listeria comprenant un système d'expression de minigènes codant pour des peptides, et leurs procédés d'utilisation |
| MX2017015149A (es) * | 2015-05-26 | 2018-03-28 | Advaxis Inc | Inmunoterapia personalizada basada en vectores de suministro y usos de esta. |
| ES2970865T3 (es) | 2015-12-16 | 2024-05-31 | Gritstone Bio Inc | Identificación, fabricación y uso de neoantígenos |
| US11253580B2 (en) | 2016-01-07 | 2022-02-22 | Duke University | Cancer vaccines and methods of delivery |
| US11224665B2 (en) | 2016-10-05 | 2022-01-18 | Duke University | Mitochondrial antiviral signaling (MAVS) protein compositions and methods of using the same |
| US10487143B2 (en) | 2016-10-05 | 2019-11-26 | Duke University | Vaccines against HER3 antigens and methods of using the same |
| CA3035591A1 (en) | 2016-11-30 | 2018-06-07 | Advaxis, Inc. | Immunogenic compositions targeting recurrent cancer mutations and methods of use thereof |
| AU2018336988B2 (en) | 2017-09-19 | 2023-06-22 | Advaxis, Inc. | Compositions and methods for lyophilization of bacteria or Listeria strains |
| EP4576103A3 (en) | 2017-10-10 | 2025-08-27 | Gritstone bio, Inc. | Neoantigen identification using hotspots |
| CN111630602A (zh) | 2017-11-22 | 2020-09-04 | 磨石肿瘤生物技术公司 | 减少新抗原的接合表位呈递 |
| AU2019231783B2 (en) | 2018-03-09 | 2023-11-16 | Advaxis, Inc. | Compositions and methods for evaluating attenuation and infectivity of Listeria strains |
| US20210239681A1 (en) | 2018-04-27 | 2021-08-05 | Advaxis, Inc. | Compositions and methods for evaluating potency of listeria-based immunotherapeutics |
| EP4168593A4 (en) | 2020-06-23 | 2024-11-27 | The Regents of the University of Colorado, a body corporate | METHODS FOR DIAGNOSIS OF RESPIRATORY PATHOGENS AND PREDICTION OF EVOLUTIONS ASSOCIATED WITH COVID-19 |
Family Cites Families (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458066A (en) * | 1980-02-29 | 1984-07-03 | University Patents, Inc. | Process for preparing polynucleotides |
| US7794729B2 (en) * | 1994-11-08 | 2010-09-14 | The Trustees Of The University Of Pennsylvania | Methods and compositions for immunotherapy of cancer |
| US7662396B2 (en) * | 2001-03-26 | 2010-02-16 | The Trustees Of The University Of Pennsylvania | Compositions and methods for enhancing the immunogenicity of antigens |
| US8114414B2 (en) | 1994-11-08 | 2012-02-14 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treatment of cervical cancer |
| US7820180B2 (en) * | 2004-09-24 | 2010-10-26 | The Trustees Of The University Of Pennsylvania | Listeria-based and LLO-based vaccines |
| AU698739B2 (en) | 1995-06-06 | 1998-11-05 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
| US5985662A (en) | 1995-07-13 | 1999-11-16 | Isis Pharmaceuticals Inc. | Antisense inhibition of hepatitis B virus replication |
| US5922583A (en) * | 1995-10-17 | 1999-07-13 | Biostar Inc. | Methods for production of recombinant plasmids |
| US6740506B2 (en) * | 1995-12-07 | 2004-05-25 | Diversa Corporation | End selection in directed evolution |
| KR100589449B1 (ko) * | 1997-04-17 | 2006-06-14 | 세키스이가가쿠 고교가부시키가이샤 | 전자회로부품 |
| US6099848A (en) | 1997-11-18 | 2000-08-08 | The Trustees Of The University Of Pennsylvania | Immunogenic compositions comprising DAL/DAT double-mutant, auxotrophic, attenuated strains of Listeria and their methods of use |
| US7198920B1 (en) * | 1999-01-29 | 2007-04-03 | Corika Corporation | HER-2/neu fusion proteins |
| US6855320B2 (en) * | 2000-03-29 | 2005-02-15 | The Trustees Of The University Of Pennsylvania | Fusion of non-hemolytic, truncated form of listeriolysin O to antigens to enhance immunogenicity |
| US7794728B2 (en) | 2002-05-29 | 2010-09-14 | The Regents Of The University Of California | Attenuated Listeria spp. and methods for using the same |
| EP1408048A1 (en) | 2002-10-07 | 2004-04-14 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Vaccines of enhanced immunogenicity, and methods for preparing such vaccines |
| US8337861B2 (en) * | 2003-01-09 | 2012-12-25 | The Trustees Of The University Of Pennsylvania | Compositions, methods and kits for enhancing the immunogenicity of a bacterial vaccine vector |
| DE10310261A1 (de) * | 2003-03-05 | 2004-09-23 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Identifizierung von Antigen-Epitopen |
| EP1682173A4 (en) * | 2003-10-15 | 2007-10-31 | Medimmune Inc | EPHA2 VACCINE ON LISTERIA BASE |
| US7855064B2 (en) * | 2004-08-13 | 2010-12-21 | The Trustees Of The University Of Pennsylvania | Antibiotic resistance free vaccines and methods for constructing and using same |
| PT2942391T (pt) | 2004-08-13 | 2018-10-09 | Univ Pennsylvania | Métodos de produção de vacinas não resistentes aos antibióticos |
| WO2007061848A2 (en) | 2005-11-17 | 2007-05-31 | The Trustees Of The University Of Pennsylvania | Methods for producing, growing, and preserving listeria vaccine vectors |
| US20070207171A1 (en) * | 2006-03-01 | 2007-09-06 | Cerus Corporation | Engineered listeria and methods of use thereof |
| US8268326B2 (en) * | 2006-08-15 | 2012-09-18 | The Trustees Of The University Of Pennsylvania | Compositions comprising HMW-MAA and fragments thereof, and methods of use thereof |
| WO2008130551A2 (en) | 2007-04-16 | 2008-10-30 | The Trustees Of The University Of Pennsylvania | Antibiotic resistance free listeria strains and methods for constructing and using same |
| US9017660B2 (en) * | 2009-11-11 | 2015-04-28 | Advaxis, Inc. | Compositions and methods for prevention of escape mutation in the treatment of Her2/neu over-expressing tumors |
| US20110129499A1 (en) * | 2008-05-19 | 2011-06-02 | Paulo Maciag | Dual delivery system for heterologous antigens |
| JP5985397B2 (ja) | 2009-11-11 | 2016-09-06 | アドバクシス インコーポレイテッド | 組換えリステリア株およびそれを含む免疫原性組成物 |
| WO2011100754A1 (en) * | 2010-02-15 | 2011-08-18 | The Trustees Of The University Of Pennsylvania | Live listeria-based vaccines for central nervous system therapy |
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| EP2498808A4 (en) | 2014-01-08 |
| US20110142791A1 (en) | 2011-06-16 |
| JP2013526837A (ja) | 2013-06-27 |
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