Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis

Tanner S. Miest, Koon Chu Yaiw, Marie Frenzke, Johanna Lampe, Andrew W. Hudacek, Christoph Springfeld, Veronika Von Messling, Guy Ungerechts, Roberto Cattaneo

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Measles virus (MV) is a promising vector for cancer therapy and multivalent vaccination, but high prevalence of pre-existing neutralizing antibodies may reduce therapeutic efficacy, particularly following systemic administration. MV has only one serotype, but here we show that its envelope glycoproteins can be exchanged with those of the closely related canine distemper virus (CDV), generating a chimeric virus capable of escaping neutralization. To target its entry, we displayed on the CDV attachment protein a single-chain antibody specific for a designated receptor. To enhance oncolytic efficacy we armed the virus with a prodrug convertase gene capable of locally activating chemotherapeutic prodrugs. The new virus achieved high titers, was genetically stable, and was resistant to neutralization by sera from both MV-immunized mice and MV-immune humans. The new virus targeted syngeneic murine tumor cells expressing the designated receptor implanted in immunocompetent mice, and synergized with a chemotherapeutic prodrug in a model of oncolysis. Importantly, the chimeric MV remained oncolytic when administered systemically even in the presence of anti-MV antibodies capable of abrogating the therapeutic efficacy of the parental, nonshielded MV. This work shows that targeting, arming, and shielding can be combined to generate a tumor-specific, neutralization-resistant virus that can synergize with chemotherapeutics.

Original languageEnglish (US)
Pages (from-to)1813-1820
Number of pages8
JournalMolecular Therapy
Volume19
Issue number10
DOIs
StatePublished - Oct 2011

Fingerprint

Measles virus
Viruses
Prodrugs
Canine Distemper Virus
Virus Attachment
Single-Chain Antibodies
Neoplasms
Neutralizing Antibodies
Glycoproteins
Vaccination
Therapeutics
Antibodies
Serum
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Genetics
  • Drug Discovery
  • Pharmacology

Cite this

Miest, T. S., Yaiw, K. C., Frenzke, M., Lampe, J., Hudacek, A. W., Springfeld, C., ... Cattaneo, R. (2011). Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis. Molecular Therapy, 19(10), 1813-1820. https://doi.org/10.1038/mt.2011.92

Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis. / Miest, Tanner S.; Yaiw, Koon Chu; Frenzke, Marie; Lampe, Johanna; Hudacek, Andrew W.; Springfeld, Christoph; Von Messling, Veronika; Ungerechts, Guy; Cattaneo, Roberto.

In: Molecular Therapy, Vol. 19, No. 10, 10.2011, p. 1813-1820.

Research output: Contribution to journalArticle

Miest, TS, Yaiw, KC, Frenzke, M, Lampe, J, Hudacek, AW, Springfeld, C, Von Messling, V, Ungerechts, G & Cattaneo, R 2011, 'Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis', Molecular Therapy, vol. 19, no. 10, pp. 1813-1820. https://doi.org/10.1038/mt.2011.92
Miest TS, Yaiw KC, Frenzke M, Lampe J, Hudacek AW, Springfeld C et al. Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis. Molecular Therapy. 2011 Oct;19(10):1813-1820. https://doi.org/10.1038/mt.2011.92
Miest, Tanner S. ; Yaiw, Koon Chu ; Frenzke, Marie ; Lampe, Johanna ; Hudacek, Andrew W. ; Springfeld, Christoph ; Von Messling, Veronika ; Ungerechts, Guy ; Cattaneo, Roberto. / Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis. In: Molecular Therapy. 2011 ; Vol. 19, No. 10. pp. 1813-1820.
@article{a70469f90f8b4675918a28fc5e55586e,
title = "Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis",
abstract = "Measles virus (MV) is a promising vector for cancer therapy and multivalent vaccination, but high prevalence of pre-existing neutralizing antibodies may reduce therapeutic efficacy, particularly following systemic administration. MV has only one serotype, but here we show that its envelope glycoproteins can be exchanged with those of the closely related canine distemper virus (CDV), generating a chimeric virus capable of escaping neutralization. To target its entry, we displayed on the CDV attachment protein a single-chain antibody specific for a designated receptor. To enhance oncolytic efficacy we armed the virus with a prodrug convertase gene capable of locally activating chemotherapeutic prodrugs. The new virus achieved high titers, was genetically stable, and was resistant to neutralization by sera from both MV-immunized mice and MV-immune humans. The new virus targeted syngeneic murine tumor cells expressing the designated receptor implanted in immunocompetent mice, and synergized with a chemotherapeutic prodrug in a model of oncolysis. Importantly, the chimeric MV remained oncolytic when administered systemically even in the presence of anti-MV antibodies capable of abrogating the therapeutic efficacy of the parental, nonshielded MV. This work shows that targeting, arming, and shielding can be combined to generate a tumor-specific, neutralization-resistant virus that can synergize with chemotherapeutics.",
author = "Miest, {Tanner S.} and Yaiw, {Koon Chu} and Marie Frenzke and Johanna Lampe and Hudacek, {Andrew W.} and Christoph Springfeld and {Von Messling}, Veronika and Guy Ungerechts and Roberto Cattaneo",
year = "2011",
month = "10",
doi = "10.1038/mt.2011.92",
language = "English (US)",
volume = "19",
pages = "1813--1820",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Envelope-chimeric entry-targeted measles virus escapes neutralization and achieves oncolysis

AU - Miest, Tanner S.

AU - Yaiw, Koon Chu

AU - Frenzke, Marie

AU - Lampe, Johanna

AU - Hudacek, Andrew W.

AU - Springfeld, Christoph

AU - Von Messling, Veronika

AU - Ungerechts, Guy

AU - Cattaneo, Roberto

PY - 2011/10

Y1 - 2011/10

N2 - Measles virus (MV) is a promising vector for cancer therapy and multivalent vaccination, but high prevalence of pre-existing neutralizing antibodies may reduce therapeutic efficacy, particularly following systemic administration. MV has only one serotype, but here we show that its envelope glycoproteins can be exchanged with those of the closely related canine distemper virus (CDV), generating a chimeric virus capable of escaping neutralization. To target its entry, we displayed on the CDV attachment protein a single-chain antibody specific for a designated receptor. To enhance oncolytic efficacy we armed the virus with a prodrug convertase gene capable of locally activating chemotherapeutic prodrugs. The new virus achieved high titers, was genetically stable, and was resistant to neutralization by sera from both MV-immunized mice and MV-immune humans. The new virus targeted syngeneic murine tumor cells expressing the designated receptor implanted in immunocompetent mice, and synergized with a chemotherapeutic prodrug in a model of oncolysis. Importantly, the chimeric MV remained oncolytic when administered systemically even in the presence of anti-MV antibodies capable of abrogating the therapeutic efficacy of the parental, nonshielded MV. This work shows that targeting, arming, and shielding can be combined to generate a tumor-specific, neutralization-resistant virus that can synergize with chemotherapeutics.

AB - Measles virus (MV) is a promising vector for cancer therapy and multivalent vaccination, but high prevalence of pre-existing neutralizing antibodies may reduce therapeutic efficacy, particularly following systemic administration. MV has only one serotype, but here we show that its envelope glycoproteins can be exchanged with those of the closely related canine distemper virus (CDV), generating a chimeric virus capable of escaping neutralization. To target its entry, we displayed on the CDV attachment protein a single-chain antibody specific for a designated receptor. To enhance oncolytic efficacy we armed the virus with a prodrug convertase gene capable of locally activating chemotherapeutic prodrugs. The new virus achieved high titers, was genetically stable, and was resistant to neutralization by sera from both MV-immunized mice and MV-immune humans. The new virus targeted syngeneic murine tumor cells expressing the designated receptor implanted in immunocompetent mice, and synergized with a chemotherapeutic prodrug in a model of oncolysis. Importantly, the chimeric MV remained oncolytic when administered systemically even in the presence of anti-MV antibodies capable of abrogating the therapeutic efficacy of the parental, nonshielded MV. This work shows that targeting, arming, and shielding can be combined to generate a tumor-specific, neutralization-resistant virus that can synergize with chemotherapeutics.

UR - http://www.scopus.com/inward/record.url?scp=80053571003&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053571003&partnerID=8YFLogxK

U2 - 10.1038/mt.2011.92

DO - 10.1038/mt.2011.92

M3 - Article

C2 - 21610701

AN - SCOPUS:80053571003

VL - 19

SP - 1813

EP - 1820

JO - Molecular Therapy

JF - Molecular Therapy

SN - 1525-0016

IS - 10

ER -