Preferential targeting of vesicular stomatitis virus to breast cancer cells

Vesicular stomatitis virus (VSV) is a candidate for development for cancer therapy. We created a recombinant replicating VSV (rrVSV) with an altered surface protein that targeted preferentially to breast cancer cells. The rrVSV genome contained a single glycoprotein (gp) gene derived from Sindbis vi...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2004-12, Vol.330 (1), p.24-33
Main Authors: Bergman, Ira, Whitaker-Dowling, Patricia, Gao, Yanhua, Griffin, Judith A.
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
ANTIBODIES
Breast cancer
Breast Neoplasms - virology
Cell Line, Tumor
Female
GENE THERAPY
GENES
Genome, Viral
GLYCOPROTEINS
GROWTH FACTORS
Her2/neu
Humans
MAMMARY GLANDS
MICE
Oncolytic virus
OSTEOSARCOMAS
RECEPTORS
Sindbis virus
SPECIFICITY
Vesicular stomatitis Indiana virus - genetics
Vesicular stomatitis Indiana virus - isolation & purification
Vesicular stomatitis Indiana virus - physiology
Vesicular stomatitis virus
Virus Replication
VIRUSES
VSV
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Summary:Vesicular stomatitis virus (VSV) is a candidate for development for cancer therapy. We created a recombinant replicating VSV (rrVSV) with an altered surface protein that targeted preferentially to breast cancer cells. The rrVSV genome contained a single glycoprotein (gp) gene derived from Sindbis virus. This gene expressed a chimeric Sindbis E2 binding gp and the native Sindbis E1 fusion gp. The chimeric E2 binding gp, called Sindbis-SCA-erbb2, was modified to reduce its native binding function and to contain a single chain antibody (SCA) with specificity for the human epidermal growth factor receptor Her2/neu protein, erbb2. These viruses selectively infected, replicated in and killed cells expressing erbb2. The titer of rrVSV on SKBR3 cells, a human breast cancer cell line which highly expresses erbb2 was 3.1 × 10 7/ml compared with a titer of 7.3 × 10 5/ml on 143 cells, a human osteosarcoma cell line which does not express erbb2. The titer of rrVSV on D2F2/E2 cells, a mouse mammary cancer cell line stably transfected to express human erbb2 was 2.46 × 10 6/ml compared with a titer of 5 × 10 4/ml on the parent D2F2 cells which do not express erbb2. When titered on erbb2-negative cells, non-replicating pseudotype VSV coated with Sindbis-SCA-erbb2 had
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2004.06.048