| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Department of Microbiology and Immunology and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida
Vesicular stomatitis virus (VSV) has recently been demonstrated to exhibit significant oncolytic capabilities against a wide variety of tumor models in vitro and in vivo. To potentially enhance the oncolytic effect, we generated a novel recombinant VSV (rVSV) that expressed the fusion suicide gene Escherichia coli cytosine deaminase (CD)/uracil phosphoribosyltransferase (UPRT). rVSV encoding the CD/UPRT fusion gene (VSV-C:U) exhibited normal growth properties and generated high levels of biologically active CD/UPRT that could catalyze the modification of 5-fluorocytosine into chemotherapeutic 5-fluorouracil (5-FU), which exhibited considerable bystander effect. Intratumoral inoculation of VSV-C:U in the presence of the systemically administered prodrug 5-fluorocytosine produced statistically significant reductions in the malignant growth of syngeneic lymphoma (A20) or mammary carcinoma (TSA) in BALB/c mice compared with rVSV treatments or with control 5-FU alone. Aside from detecting prolonged therapeutic levels of 5-FU in VSV-C:U-treated animals harboring TSA tumors and enhancing bystander killing of tumor cells, we demonstrated marked activation of IFN-
-secreting cytotoxic T cells by enzyme-linked immunospot analysis that may have also facilitated tumor killing. In conclusion, the insertion of the fusion CD/UPRT suicide gene potentiates the oncolytic efficiency of VSV by generating a strong bystander effect and by contributing to the activation of the immune system against the tumor without detrimentally altering the kinetics of virus-mediated oncolysis and may be useful in the treatment of malignant disease.
This article has been cited by other articles:
|
|
 |
|
  B. L. Carey, M. Ahmed, S. Puckett, and D. S. Lyles Early Steps of the Virus Replication Cycle Are Inhibited in Prostate Cancer Cells Resistant to Oncolytic Vesicular Stomatitis Virus J. Virol., December 15, 2008; 82(24): 12104 - 12115. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wu, X. Lun, H. Zhou, L. Wang, B. Sun, J. C. Bell, J. W. Barrett, G. McFadden, J. A. Biegel, D. L. Senger, et al. Oncolytic Efficacy of Recombinant Vesicular Stomatitis Virus and Myxoma Virus in Experimental Models of Rhabdoid Tumors Clin. Cancer Res., February 15, 2008; 14(4): 1218 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Diaz, F. Galivo, T. Kottke, P. Wongthida, J. Qiao, J. Thompson, M. Valdes, G. Barber, and R. G. Vile Oncolytic Immunovirotherapy for Melanoma Using Vesicular Stomatitis Virus Cancer Res., March 15, 2007; 67(6): 2840 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Toyoda, J. Yin, S. Mueller, E. Wimmer, and J. Cello Oncolytic Treatment and Cure of Neuroblastoma by a Novel Attenuated Poliovirus in a Novel Poliovirus-Susceptible Animal Model Cancer Res., March 15, 2007; 67(6): 2857 - 2864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lun, D. L. Senger, T. Alain, A. Oprea, K. Parato, D. Stojdl, B. Lichty, A. Power, R. N. Johnston, M. Hamilton, et al. Effects of Intravenously Administered Recombinant Vesicular Stomatitis Virus (VSV{Delta}M51) on Multifocal and Invasive Gliomas. J Natl Cancer Inst, November 1, 2006; 98(21): 1546 - 1557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Chiocca Oncolytic Viral Therapeutics Based on Herpes Simplex Virus Type I Am. Assoc. Cancer Res. Educ. Book, April 1, 2005; 2005(1): 139 - 140. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
