title: Enhancement of the antitumor effect on combination therapy of an anticancer drug and its antibody against carcinoembryonic antigen.
abstract: BACKGROUND
  Carcinoembryonic antigen (CEA) is frequently overexpressed in various types of human cancers and is associated with cell adhesion. There are three possible mechanisms of cancer therapy that employ anti-CEA antibody (Ab): Ab-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) or the prevention of CEA interaction with the extracellular matrix and/or intercellular adhesion molecules resulting in anoikis. In this study, the effect of C2-74, a human anti-CEA monoclonal Ab was evaluated.
  
  
  METHODS
  ADCC, CDC and anoikis assays in combination with C2-74 and an anticancer drug (5-fluorouracil or cisplatin) were investigated using tumor cell lines (MKN-45, MKN-74 and KATO III). In the anoikis assay, other human anti-CEA Abs and mouse anti-CEA-related cell adhesion molecule 6 Abs were also investigated using HLC-1 cells.
  
  
  RESULTS
  Additive cytotoxicity was observed when the anticancer drug and C2-74 on tumor cells were combined in the CDC assays, whereas in the anoikis assay, no such additive effect was observed. Anti-CEA-related cell adhesion molecule 6 Abs, but not anti-CEA Abs, accelerated anoikis in HLC-1 cells.
  
  
  CONCLUSIONS
  A mechanism for the additive antitumor effect when an anticancer drug and C2-74 are combined is indicated mainly by CDC activity but is irrelevant to anoikis in tumor cells.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. shiba-h@fukuoka-u.ac.jp
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Shibaguchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tsuru
authors.forename: Motomu
authors.initials: M
authors.lastname: Kuroki
authors.forename: Masahide
authors.initials: M
authors.lastname: Kuroki
mesh_terms: D023102:Anoikis / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003175:Complement C2 / Q000276:immunology; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D003175:Complement C2; D002945:Cisplatin; D005472:Fluorouracil