Preferential targeting of vesicular stomatitis virus to breast cancer cells
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260 (United States) and Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260 (United States) and Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260 (United States)
- Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260 (United States)
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260 (United States)
- Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213 (United States)
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 x 10{sup 7}/ml compared with a titer of 7.3 x 10{sup 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 x 10{sup 6}/ml compared with a titer of 5 x 10{sup 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 <3% the titer of pseudotype VSV coated with wild type Sindbis gp indicating that the chimeric Sindbis gp had severely impaired binding to the natural receptor. Analysis of the protein composition of the rrVSV found low expression of the modified Sindbis gp on the virus.
- OSTI ID:
- 20637179
- Journal Information:
- Virology, Vol. 330, Issue 1; Other Information: DOI: 10.1016/j.virol.2004.06.048; PII: S0042-6822(04)00456-8; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0042-6822
- Country of Publication:
- United States
- Language:
- English
Similar Records
Engineered Exosomes for Targeted Transfer of siRNA to HER2 Positive Breast Cancer Cells
Ebolavirus Glycoprotein Fc Fusion Protein Protects Guinea Pigs against Lethal Challenge