title: Tumor specificity and in vivo targeting of an antibody against exon 9 deleted E-cadherin in gastric cancer.
abstract: OBJECTIVE
  The aim of this study was to evaluate the possibility of using a monoclonal antibody against exon 9 deleted E-cadherin (E-cad delta 9-1) for immunotherapy of gastric cancer.
  
  
  METHODS
  Among nine human diffuse-type gastric cancer cell lines, we selected a cell line expressing exon 9 deleted E-cadherin (HSC-45M2) by direct sequencing. Tumor specificity and tumor specific in vivo targeting of E-cad delta 9-1 were evaluated in nude mouse bearing a tumor derived from HSC-45M2 cell line by immunohistochemical staining. The expression rate of E-cad delta 9-1 was evaluated in 299 gastric cancer patients, and in positive cases, the mutational status of E-cadherin exon 9 was examined.
  
  
  RESULTS
  Immunohistochemical staining of various tissues from nude mice showed that only tumor tissue reacted with E-cad delta 9-1. However, immunohistochemical staining of the same tissues after systemic injection of E-cad delta 9-1 showed that reticuloendothelial and hypervascular organs reacted with E-cad delta 9-1, but tumor tissue showed only a slight reaction. Evaluation of the reactivity of 299 gastric cancer patients to E-cad delta 9-1 showed that 4.8% (9/187) of patients, who all had diffuse- or mixed-type gastric cancers, reacted positively, but none of the 112 intestinal-type gastric cancer patients reacted positively. Two of 9 patients (22%) with positive staining to E-cad delta 9-1 were confirmed to have mutant forms of E-cadherin exon 9.
  
  
  CONCLUSIONS
  Considering that E-cad delta 9-1 showed good tumor specificity and that some diffuse-type gastric cancers were immunopositive to it, this antibody could be a candidate therapeutic antibody against gastric cancers that express mutant E-cadherin.
authors.affiliation: Cancer Research Institute, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Republic of Korea.
authors.forename: Hyuk-Joon
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Keun
authors.initials: K
authors.lastname: Hur
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Becker
authors.forename: Kuhn Uk
authors.initials: KU
authors.lastname: Lee
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D015820:Cadherins / Q000235:genetics* / Q000276:immunology*; D045744:Cell Line, Tumor; D005091:Exons; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012680:Sensitivity and Specificity; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D015820:Cadherins