Efficacy of a genetically-modified Salmonella typhimurium in an orthotopic human pancreatic cancer in nude mice.
We report here a tumor-targeting strategy for pancreatic cancer using a modified auxotrophic strain of Salmonella typhimurium. The genetically-modified strain of S. typhimurium requires the amino acids arginine and leucine. These mutations preclude growth in normal tissue but do not reduce bacterial virulence in tumor cells. The tumor-targeting strain of S. typhimurium, termed A1-R and expressing green fluorescent protein (GFP), was administered to an orthotopic human pancreatic tumor expressing red fluorescent protein (RFP) in nude mice. After 7 days of treatment, the pancreatic cancer had regressed without the need of chemotherapy or any other treatment. This new strategy demonstrates the clinical potential of bacterial targeting for pancreatic cancer.
Nagakura
Chisa
C
AntiCancer, Inc., San Diego, CA 92111, U.S.A.
Hayashi
Katsuhiro
K
Zhao
Ming
M
Yamauchi
Kensuke
K
Yamamoto
Norio
N
Tsuchiya
Hiroyuki
H
Tomita
Katsuro
K
Bouvet
Michael
M
Hoffman
Robert M
RM
D000818:Animals; D001120:Arginine / Q000378:metabolism; D045744:Cell Line, Tumor; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007930:Leucine / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D030781:Organisms, Genetically Modified; D010190:Pancreatic Neoplasms / Q000382:microbiology* / Q000628:therapy*; D012486:Salmonella typhimurium / Q000502:physiology*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D049452:Green Fluorescent Proteins; D001120:Arginine; D007930:Leucine