Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus

Qian Zhang, Yong A. Yu, Ena Wang, Nanhai Chen, Robert L. Danner, Peter J. Munson, Francesco M. Marincola, Aladar A. Szalay

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Previously, we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase-Aequorea green fluorescent protein fusion, β-galactosidase, and β-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase) and A56R (encoding hemagglutinin) loci of the viral genome, respectively. I.v. injections of GLV-1h68 (1 × 10 7 plaque-forming unit per mouse) into nude mice with established (∼300-500 mm 3) s.c. GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity, and oncolytic efficacy. GLV-1h68 showed an enhanced tumor targeting specificity and much reduced toxicity compared with its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of IFN-stimulated genes (STAT-1 and IRF-7), cytokines, chemokines, and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers.

Original languageEnglish
Pages (from-to)10038-10046
Number of pages9
JournalCancer Research
Volume67
Issue number20
DOIs
Publication statusPublished - 15 Oct 2007
Externally publishedYes

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Oncolytic Viruses
Vaccinia virus
Nude Mice
Breast Neoplasms
Light
Neoplasms
Renilla Luciferases
Galactosidases
Thymidine Kinase
Viral Genome
Gene Fusion
Glucuronidase
Hemagglutinins
Green Fluorescent Proteins
Transcriptome
Chemokines
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus. / Zhang, Qian; Yu, Yong A.; Wang, Ena; Chen, Nanhai; Danner, Robert L.; Munson, Peter J.; Marincola, Francesco M.; Szalay, Aladar A.

In: Cancer Research, Vol. 67, No. 20, 15.10.2007, p. 10038-10046.

Research output: Contribution to journalArticle

Zhang, Qian ; Yu, Yong A. ; Wang, Ena ; Chen, Nanhai ; Danner, Robert L. ; Munson, Peter J. ; Marincola, Francesco M. ; Szalay, Aladar A. / Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus. In: Cancer Research. 2007 ; Vol. 67, No. 20. pp. 10038-10046.
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