title: Immunogene therapy against colon cancer metastasis using an adenovirus vector expressing CD40 ligand.
abstract: BACKGROUND
  Colon cancer is one of the most common cancers worldwide, and liver metastasis is a poor prognostic factor for all types of digestive cancers, including colon cancer. We studied CD40 ligand (CD40L)-mediated immunogene therapy for metastatic liver cancer in rats.
  
  
  METHODS
  We studied whether in vitro infection of a rat colon cancer cell line (RCN9) with an adenoviral-vector that expresses the CD40L (AxCAmCD40L) induced CD40L expression. In vivo to confirm the antitumor effect induced by AxCAmCD40L, the tumor cells that had been transduced by AxCAmCD40L were implanted into the subcutaneous tissues of syngenic rats (prevention model) or AxCAmCD40L was injected into the tumor tissues of the rats (treatment model). Furthermore, immune cells including NK cells, cytotoxic T cells, and tumor-specific antibodies induced by AxCAmCD40L were examined.
  
  
  RESULTS
  Immunogene therapy using AxCAmCD40L suppressed the tumor growth strongly or reduced tumor size in the prevention model and treatment model. NK cells, cytotoxic T cells, and tumor-specific antibodies contributed to this antitumor effect in both groups.
  
  
  CONCLUSIONS
  These observations suggest that CD40L-mediated immunogene therapy for metastatic colon cancer in the liver and lungs is effective and is mediated by the activation of both the cellular and humoral immune systems.
authors.affiliation: Department of Surgery, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan. pooh-tom@jikei.ac.jp
authors.forename: Tomonori
authors.initials: T
authors.lastname: Iida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shiba
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Misawa
authors.forename: Toya
authors.initials: T
authors.lastname: Ohashi
authors.forename: Yoshikatsu
authors.initials: Y
authors.lastname: Eto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yanaga
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D023201:CD40 Ligand / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D023201:CD40 Ligand