Tumor specificity and in vivo targeting of an antibody against exon 9 deleted E-cadherin in gastric cancer.
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.
Lee
Hyuk-Joon
HJ
Cancer Research Institute, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul 110-744, Republic of Korea.
Lee
Hye Seung
HS
Hur
Keun
K
Kim
Woo Ho
WH
Yanagihara
Kazuyoshi
K
Becker
Karl-Friedrich
KF
Lee
Kuhn Uk
KU
Yang
Han-Kwang
HK
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
D000911:Antibodies, Monoclonal; D015820:Cadherins