Abstract
Suicide genes (SG) can be viewed as negatively selectable marker genes. Their gene products convert otherwise nontoxic prodrugs (PD) into cytotoxic metabolites. The enzymatic conversion leads to high levels of the activated toxic drug within genetically modified cells and ultimately kills the cells. Several studies have shown that when SG-expressing tumor cells are mixed with parental, nongenetically modified cells, prodrug treatment induces toxic effects in the nonmodified cells. This phenomenon has been termed “bystander (killing) effect.”
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bonini, C., Ferrari, G., Verzeletti, S., et al. (1997) HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 276, 1719–1724.
Yee, C., Thompson, J. A., Roche, P., et al. (2000) Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of T cell-mediated vitiligo. J. Exp. Med. 192, 1637–1644.
Rogulski, K. R., Kim, J. H., Kim, S. H., and Freytag, S. O. (1997) Glioma cells transduced with an Escherichia coli CD/HSV-1 TK fusion gene exhibit enhanced metabolic suicide and radiosensitivity. Hum. Gene Ther. 8, 73–85.
Uckert, W., Kammertöns, T., Haack, K., et al. (1998) Double suicide gene (cytosine deaminase and herpes simplex virus thymidine kinase) but not single gene transfer allows reliable elimination of tumor cells in vivo. Hum. Gene Ther. 9, 855–865.
Kammertöns, T., Gelbmann, W., Karle, P., et al. (2000) Combined chemotherapy of murine mammary tumors by local activation of the prodrugs ifosfamide and 5-fluorocytosin. Cancer Gene Ther. 7, 629–636.
Cosset, F.-L., Takeuchi, Y., Battini, J. L., Weiss, R. A., and Collins, M. K. (1995) High-titer packaging cells producing recombinant retrovirus resistant to human serum. J. Virol. 69, 7400–7436.
Crandel, R. A., Fabricant, C. G., and Nelson, R. W. (1973) Development, characterization, and viral susceptibility of a feline (Felis catus) renal cell line (CRFK). In Vitro 9, 176–185.
Nanni, P., de Giovanni, C., Lollini, P. L., Nicoletti, G., and Prodi, G. (1983) TS/A: a new metastasizing cell line from BALB/c spontaneous mammary adenocarcinoma. Clin. Exp. Metastasis 1, 373–380.
Löhr, M., Müller, P., Karle, P., et al. (1998) Targeted chemotherapy by intratumoral injection of encapsulated cells engineered to produce CYP2B1, an ifosfamide activating cytochrome P450. Gene Ther. 5, 1070–1078.
Dautzenberg, H., Schuldt, U., Grasnick, G., et al. (1999) Development of cellulose sulphate based polyelectrolyte complex microcapsules for medical applications. Ann. NY Acad. Sci. 875, 46–63.
Uckert, W., Pedersen, L., and Günzburg, W. (2000) Green fluorescent protein retroviral vector: generation of high-titer producer cells and virus supernatant, in Gene Therapy of Cancer: Methods and Protocols (Walther, W. and Stein, U., eds.), Humana, Totowa, NJ, pp. 275–285.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Humana Press Inc.
About this protocol
Cite this protocol
Uckert, W., Salmons, B., Beltinger, C., Günzburg, W.H., Kammertöns, T. (2004). Combination Suicide Gene Therapy. In: Springer, C.J. (eds) Suicide Gene Therapy. Methods in Molecular Medicine™, vol 90. Humana Press. https://doi.org/10.1385/1-59259-429-8:345
Download citation
DOI: https://doi.org/10.1385/1-59259-429-8:345
Publisher Name: Humana Press
Print ISBN: 978-0-89603-971-1
Online ISBN: 978-1-59259-429-0
eBook Packages: Springer Protocols