PEGylation of vesicular stomatitis virus extends virus persistence in blood circulation of passively immunized mice
- PMID: 23325695
- PMCID: PMC3624195
- DOI: 10.1128/JVI.02832-12
PEGylation of vesicular stomatitis virus extends virus persistence in blood circulation of passively immunized mice
Erratum in
- J Virol. 2015 Feb;89(4):2453
Abstract
We are developing oncolytic vesicular stomatitis viruses (VSVs) for systemic treatment of multiple myeloma, an incurable malignancy of antibody-secreting plasma cells that are specifically localized in the bone marrow. One of the presumed advantages for using VSV as an oncolytic virus is that human infections are rare and preexisting anti-VSV immunity is typically lacking in cancer patients, which is very important for clinical success. However, our studies show that nonimmune human and mouse serum can neutralize clinical-grade VSV, reducing the titer by up to 4 log units in 60 min. In addition, we show that neutralizing anti-VSV antibodies negate the antitumor efficacy of VSV, a concern for repeat VSV administration. We have investigated the potential use of covalent modification of VSV with polyethylene glycol (PEG) or a function-spacer-lipid (FSL)-PEG construct to inhibit serum neutralization and to limit hepatosplenic sequestration of systemically delivered VSV. We report that in mice passively immunized with neutralizing anti-VSV antibodies, PEGylation of VSV improved the persistence of VSV in the blood circulation, maintaining a more than 1-log-unit increase in VSV genome copies for up to 1 h compared to the genome copy numbers for the non-PEGylated virus, which was mostly cleared within 10 min after intravenous injection. We are currently investigating if this increase in PEGylated VSV circulating half-life can translate to increased virus delivery and better efficacy in mouse models of multiple myeloma.
Figures






Similar articles
-
Vesiculovirus neutralization by natural IgM and complement.J Virol. 2014 Jun;88(11):6148-57. doi: 10.1128/JVI.00074-14. Epub 2014 Mar 19. J Virol. 2014. PMID: 24648451 Free PMC article.
-
Potent systemic therapy of multiple myeloma utilizing oncolytic vesicular stomatitis virus coding for interferon-β.Cancer Gene Ther. 2012 Jul;19(7):443-50. doi: 10.1038/cgt.2012.14. Epub 2012 Apr 20. Cancer Gene Ther. 2012. PMID: 22522623 Free PMC article.
-
Xenoantigen-Dependent Complement-Mediated Neutralization of Lymphocytic Choriomeningitis Virus Glycoprotein-Pseudotyped Vesicular Stomatitis Virus in Human Serum.J Virol. 2019 Aug 28;93(18):e00567-19. doi: 10.1128/JVI.00567-19. Print 2019 Sep 15. J Virol. 2019. PMID: 31243134 Free PMC article.
-
Preclinical efficacy of oncolytic VSV-IFNβ in treating cancer: A systematic review.Front Immunol. 2023 Mar 31;14:1085940. doi: 10.3389/fimmu.2023.1085940. eCollection 2023. Front Immunol. 2023. PMID: 37063914 Free PMC article.
-
Oncotargeting by Vesicular Stomatitis Virus (VSV): Advances in Cancer Therapy.Viruses. 2018 Feb 23;10(2):90. doi: 10.3390/v10020090. Viruses. 2018. PMID: 29473868 Free PMC article. Review.
Cited by
-
Vesiculovirus neutralization by natural IgM and complement.J Virol. 2014 Jun;88(11):6148-57. doi: 10.1128/JVI.00074-14. Epub 2014 Mar 19. J Virol. 2014. PMID: 24648451 Free PMC article.
-
Potential of oncolytic viruses in the treatment of multiple myeloma.Oncolytic Virother. 2018 Feb 23;7:1-12. doi: 10.2147/OV.S136644. eCollection 2017. Oncolytic Virother. 2018. PMID: 29503813 Free PMC article. Review.
-
Oncolytic Viruses for Multiple Myeloma Therapy.Cancers (Basel). 2018 Jun 14;10(6):198. doi: 10.3390/cancers10060198. Cancers (Basel). 2018. PMID: 29903988 Free PMC article. Review.
-
Virus-Based Nanoparticles as Versatile Nanomachines.Annu Rev Virol. 2015 Nov;2(1):379-401. doi: 10.1146/annurev-virology-100114-055141. Epub 2015 Sep 25. Annu Rev Virol. 2015. PMID: 26958921 Free PMC article. Review.
-
Oncolytic viruses: how "lytic" must they be for therapeutic efficacy?Oncoimmunology. 2019 Mar 28;8(6):e1581528. doi: 10.1080/2162402X.2019.1596006. eCollection 2019. Oncoimmunology. 2019. PMID: 31069150 Free PMC article. Review.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical