title: Eradication of ovarian tumor xenografts by locoregional administration of targeted immunotherapy.
abstract: OBJECTIVE
  Oligodeoxynucleotides containing unmethylated CpG motifs (CpG-ODN) are potent activators of innate and adaptive immunity. Recognition of CpG-ODN is mediated by Toll-like receptor 9 expressed by immune cells, endothelial and epithelial cells, and fibroblasts. We examined the antitumor effect of CpG-ODN and the role of administration route on human ovarian cancers growing in the peritoneal cavity of nude mice.
  
  
  METHODS
  Mice implanted i.p. with human ovarian carcinoma cells were treated i.p., s.c., or i.v. and assessed for survival and tumor-free incidence. Peritoneal washings were analyzed for keratinocyte chemokine production and for functional and phenotypic profiles as indicators of the cell types involved in mediating the antitumor effects.
  
  
  RESULTS
  IGROV-1-bearing mice treated i.p. survived significantly longer than those treated i.v. or s.c. (P=0.0005), and nearly half of them (8 of 17) were tumor-free by the end of the experiment, a rate never achieved using a variety of chemotherapeutic drugs. High rates of tumor-free mice were observed in three other ovarian tumor xenografts treated i.p. Compared with peritoneal washings of mice treated s.c. or i.v., those from mice treated i.p. showed the highest level of serum and tissue keratinocyte chemokine, the highest number of natural killer cells and neutrophils, and the highest antiproliferative activity in vitro.
  
  
  CONCLUSIONS
  The superior antitumor effect obtained by locoregional administration of CpG-ODN in i.p. tumor-bearing mice with a limited adaptive immune response points to the importance of innate effector cells amplification at the site of tumor growth and suggests the promise of i.p. CpG-ODN in clinical trials for ovarian cancer.
authors.affiliation: Preclinical Chemotherapy and Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Michelandrea
authors.initials: M
authors.lastname: De Cesare
authors.forename: Claudia
authors.initials: C
authors.lastname: Calcaterra
authors.forename: Graziella
authors.initials: G
authors.lastname: Pratesi
authors.forename: Laura
authors.initials: L
authors.lastname: Gatti
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mènard
authors.forename: Andrea
authors.initials: A
authors.lastname: Balsari