Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Mar 28, 2008; 14(12): 1842-1850
Published online Mar 28, 2008. doi: 10.3748/wjg.14.1842
Immune-mediated anti-neoplastic effect of intratumoral RSV envelope glycoprotein expression is related to apoptotic death of tumor cells but not to the size of syncytia
Dennis Hoffmann, Thomas Grunwald, Wibke Bayer, Oliver Wildner
Dennis Hoffmann, Thomas Grunwald, Wibke Bayer, Oliver Wildner, Ruhr-University Bochum, Institute of Microbiology and Hygiene, Department of Molecular and Medical Virology, Bldg. MA, Rm. 6/40, Bochum 44801, Germany
Author contributions: Hoffmann D designed and performed the research and drafted the manuscript; Grunwald T and Bayer W contributed new reagents/analytic tools; Wildner O designed the study, analyzed the data, acquired funding and wrote the manuscript.
Correspondence to: Dr. Oliver Wildner, Ruhr-University Bochum, Institute of Microbiology and Hygiene, Department of Molecular and Medical Virology, Bldg. MA, Rm. 6/40, Bochum 44801, Germany. oliver.wildner@ruhr-uni-bochum.de
Telephone: +49-234-3227834
Fax: +49-234-3214352
Received: September 26, 2007
Revised: December 19, 2007
Published online: March 28, 2008
Abstract

AIM: To promote the development of improved tumor vaccination strategies relying on the intratumoral expression of viral fusogenic membrane proteins, we elucidated whether the size of syncytia or the way tumor cells die has an effect on the therapeutic outcome.

METHODS: In two syngeneic subcutaneous murine colon cancer models we assessed the anti-neoplastic effect on vector-treated and contralateral untreated tumors.

RESULTS: Intratumoral injection of a replication-defective adenovirus encoding respiratory syncytial virus fusion protein (RSV-F) alone (Ad.RSV-F) or together with the attachment glycoprotein RSV-G (Ad.RSV-F/G) led to a significant growth reduction of the vector-treated and contralateral untreated tumors. The treatment response was associated with a strong tumor-specific CTL response and significantly improved survival with medians of 46 d and 44 d, respectively. Intratumoral injection of Ad.RSV-G or a soluble RSV-F encoding adenovirus (Ad.RSV-Fsol) had no significant anti-neoplastic effect. The median survival of these treatment groups and of Ad.Null-treated control animals was about 30 d.

CONCLUSION: Although in vitro transduction of colon cancer cell lines with Ad.RSV-F/G resulted in about 8-fold larger syncytia than with Ad.RSV-F, the in vivo outcome was not significantly different. Transduction of murine colon cancer cell lines with Ad.RSV-F or Ad.RSV-F/G caused apoptotic cell death, in contrast to transduction with Ad.RSV-G or Ad.RSV-Fsol, suggesting an importance of the mode of cell death. Overall, these findings provide insight into improved tumor vaccination strategies relying on the intratumoral expression of viral fusogenic membrane proteins.

Keywords: Adenoviral vectors, Tumor vaccination, Fusogenic membrane protein, Colorectal cancer, Syngeneic tumor model