title: Induction of effective antitumor response after mucosal bacterial vector mediated DNA vaccination with endogenous prostate cancer specific antigen.
abstract: OBJECTIVE
  The induction of systemic immune responses against antigenic targets that are over expressed by cancer cells represents a powerful therapeutic strategy to target metastatic cancer. We generated specific antitumor immune responses in a murine model of prostate cancer by oral administration of an attenuated strain of Salmonella typhimurium containing a plasmid coding for murine prostate stem cell antigen.
  
  
  METHODS
  Trafficking of S. typhimurium SL7207 in the initial 10 hours after gavage feeding was determined using a bacterial lux expressing strain and live bioluminescence imaging. For vaccination trials male C57 BL/6 mice were gavage fed SL7207/murine prostate stem cell antigen expressing plasmid or controls twice at 2-week intervals. One week after the last feeding the mice were challenged subcutaneously with TRAMPC1 murine prostate carcinoma cells. Tumor dynamics and animal survival were recorded.
  
  
  RESULTS
  Clearance of bacterial vector from animals was complete 9 hours after feeding. Delivery of vector transformed with a firefly luciferase reporter plasmid resulted in maximal eukaryotic reporter gene expression in splenocytes 48 hours after feeding. Induction of tumor protective immunity was achieved by feeding the mice murine prostate stem cell antigen expressing plasmid bearing bacteria and greater than 50% of immunized mice remained tumor free. No significant toxicity was observed. Induction of T-helper type 1 immune responses was determined by measuring interferon-γ produced by splenocytes from vaccinated mice. When adoptively transferred to naive animals, splenocytes from vaccinated mice prevented tumor growth in 66% of challenged animals.
  
  
  CONCLUSIONS
  Endogenous prostate cancer antigen gene delivery using a bacterial vector resulted in breaking immune tolerance to murine prostate stem cell antigen and significant retardation of tumor growth.
authors.affiliation: Leslie C. Quick Jr. Laboratory, Cork Cancer Research Centre, and Department of Surgery, Mercy University Hospital, University College Cork, Cork, Ireland.
authors.forename: Sarfraz
authors.initials: S
authors.lastname: Ahmad
authors.forename: Garrett
authors.initials: G
authors.lastname: Casey
authors.forename: Michelle
authors.initials: M
authors.lastname: Cronin
authors.forename: Simon
authors.initials: S
authors.lastname: Rajendran
authors.forename: Paul
authors.initials: P
authors.lastname: Sweeney
authors.forename: Mark
authors.initials: M
authors.lastname: Tangney
authors.forename: Gerald C
authors.initials: GC
authors.lastname: O'Sullivan
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics*; D019496:Cancer Vaccines / Q000276:immunology*; D004269:DNA, Bacterial; D058851:GPI-Linked Proteins / Q000235:genetics; D015316:Genetic Therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D012486:Salmonella typhimurium
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004269:DNA, Bacterial; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C504399:Psca protein, mouse