Antitumor therapeutic effects of Salmonella typhimurium containing Flt3 Ligand expression plasmids in melanoma-bearing mouse.
An attenuated strain of Salmonella typhimurium has been tested in animals and clinically as an anticancer agent due to its in vivo tumor-targeting and tumoricidal properties. We exploited a genetically-engineered S. typhimurium harboring Flt3 Ligand (Flt3L) expression vectors as a tumoricidal agent to enhance its therapeutic efficacy. Flt3L showed tumoricidal effects when expressed in tumor cells in vitro. When melanoma-bearing mice were treated locally with Salmonella, S. typhimurim with Flt3L expression vectors inhibited tumor growth more than Salmonella controls (50% vs. 0% in tumor regression rates). Moreover, it prolonged survivals of animals without induction of memory antitumor protective responses to a parental tumor re-challenge (50% vs. 0% in survival rates). These results suggest that a genetically engineered S. typhimurium with Flt3L expression vectors has the potential to be applicable as a safer and more effective tumor-targeting and tumoricidal agent.
Yoon
Won Suck
WS
Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, SeoungBuk-gu, Seoul, Korea.
Choi
Won Cheol
WC
Sin
Jeong-Im
JI
Park
Yong Keun
YK
D000818:Animals; D045744:Cell Line, Tumor; D004269:DNA, Bacterial / Q000008:administration & dosage*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D008565:Membrane Proteins / Q000235:genetics* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000008:administration & dosage*; D012486:Salmonella typhimurium / Q000235:genetics*; D014162:Transfection / Q000379:methods*
D004269:DNA, Bacterial; D008565:Membrane Proteins; C084881:flt3 ligand protein