Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies
The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, t...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-01-01
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| Series: | Molecular Therapy: Oncolytics |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770516300638 |
| _version_ | 1818344681845555200 |
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| author | Laura Evgin Carolina S Ilkow Marie-Claude Bourgeois-Daigneault Christiano Tanese de Souza Lawton Stubbert Michael S Huh Victoria A Jennings Monique Marguerie Sergio A Acuna Brian A Keller Charles Lefebvre Theresa Falls Fabrice Le Boeuf Rebecca A Auer John D Lambris J Andrea McCart David F Stojdl John C Bell |
| author_facet | Laura Evgin Carolina S Ilkow Marie-Claude Bourgeois-Daigneault Christiano Tanese de Souza Lawton Stubbert Michael S Huh Victoria A Jennings Monique Marguerie Sergio A Acuna Brian A Keller Charles Lefebvre Theresa Falls Fabrice Le Boeuf Rebecca A Auer John D Lambris J Andrea McCart David F Stojdl John C Bell |
| author_sort | Laura Evgin |
| collection | DOAJ |
| description | The systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway. We show that this phenotype can be capitalized upon to deliver maraba virus pseudotyped with the lymphocytic choriomeningitis virus glycoprotein in a Fischer rat model in the face of neutralizing antibody through the use of complement modulators. This finding changes the understanding of the humoral immune response to arenaviruses, and also describes methodology to deliver viral vectors to their therapeutic sites of action without the interference of neutralizing antibody. |
| first_indexed | 2024-12-13T16:50:21Z |
| format | Article |
| id | doaj.art-03318fbb20d24026bc983751bf71f24d |
| institution | Directory Open Access Journal |
| issn | 2372-7705 |
| language | English |
| last_indexed | 2024-12-13T16:50:21Z |
| publishDate | 2016-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncolytics |
| spelling | doaj.art-03318fbb20d24026bc983751bf71f24d2022-12-21T23:38:02ZengElsevierMolecular Therapy: Oncolytics2372-77052016-01-013C10.1038/mto.2016.27Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodiesLaura Evgin0Carolina S Ilkow1Marie-Claude Bourgeois-Daigneault2Christiano Tanese de Souza3Lawton Stubbert4Michael S Huh5Victoria A Jennings6Monique Marguerie7Sergio A Acuna8Brian A Keller9Charles Lefebvre10Theresa Falls11Fabrice Le Boeuf12Rebecca A Auer13John D Lambris14J Andrea McCart15David F Stojdl16John C Bell17Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaToronto General Research Institute, University Health Network, Toronto, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaChildren’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USAToronto General Research Institute, University Health Network, Toronto, Ontario, CanadaDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, CanadaCenter for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, CanadaThe systemic delivery of therapeutic viruses, such as oncolytic viruses or vaccines, is limited by the generation of neutralizing antibodies. While pseudotyping of rhabdoviruses with the lymphocytic choriomeningitis virus glycoprotein has previously allowed for multiple rounds of delivery in mice, this strategy has not translated to other animal models. For the first time, we provide experimental evidence that antibodies generated against the lymphocytic choriomeningitis virus glycoprotein mediate robust complement-dependent viral neutralization via activation of the classical pathway. We show that this phenotype can be capitalized upon to deliver maraba virus pseudotyped with the lymphocytic choriomeningitis virus glycoprotein in a Fischer rat model in the face of neutralizing antibody through the use of complement modulators. This finding changes the understanding of the humoral immune response to arenaviruses, and also describes methodology to deliver viral vectors to their therapeutic sites of action without the interference of neutralizing antibody.http://www.sciencedirect.com/science/article/pii/S2372770516300638 |
| spellingShingle | Laura Evgin Carolina S Ilkow Marie-Claude Bourgeois-Daigneault Christiano Tanese de Souza Lawton Stubbert Michael S Huh Victoria A Jennings Monique Marguerie Sergio A Acuna Brian A Keller Charles Lefebvre Theresa Falls Fabrice Le Boeuf Rebecca A Auer John D Lambris J Andrea McCart David F Stojdl John C Bell Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies Molecular Therapy: Oncolytics |
| title | Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies |
| title_full | Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies |
| title_fullStr | Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies |
| title_full_unstemmed | Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies |
| title_short | Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies |
| title_sort | complement inhibition enables tumor delivery of lcmv glycoprotein pseudotyped viruses in the presence of antiviral antibodies |
| url | http://www.sciencedirect.com/science/article/pii/S2372770516300638 |
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