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Mol Ther Oncolytics. 2016 Nov 16;3:16027. eCollection 2016.

Complement inhibition enables tumor delivery of LCMV glycoprotein pseudotyped viruses in the presence of antiviral antibodies.

Author information

1
Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
2
Center for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute , Ottawa, Ontario, Canada.
3
Toronto General Research Institute, University Health Network , Toronto, Ontario, Canada.
4
Children's Hospital of Eastern Ontario Research Institute , Ottawa, Ontario, Canada.
5
Department of Pathology and Laboratory Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
6
Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; Department of Surgery, Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada.
7
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada; Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada.

Abstract

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.

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