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Journal of Cancer Research and Clinical Oncology

, Volume 133, Issue 12, pp 987–994 | Cite as

Tumor specificity and in vivo targeting of an antibody against exon 9 deleted E-cadherin in gastric cancer

  • Hyuk-Joon Lee
  • Hye Seung Lee
  • Keun Hur
  • Woo Ho Kim
  • Kazuyoshi Yanagihara
  • Karl-Friedrich Becker
  • Kuhn Uk Lee
  • Han-Kwang YangEmail author
Original Paper

Abstract

Purpose

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.

Conclusion

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.

Keywords

E-cadherin Exon 9 Mutation Monoclonal antibody Immunotherapy Gastric cancer 

Abbreviations

mAb

Monoclonal antibody

DGC

Diffuse-type gastric cancer

Notes

Acknowledgment

This study was supported by grant no. 04-2004-036 from the Seoul National University Hospital Research Fund.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Hyuk-Joon Lee
    • 1
    • 2
  • Hye Seung Lee
    • 3
  • Keun Hur
    • 1
  • Woo Ho Kim
    • 1
    • 3
  • Kazuyoshi Yanagihara
    • 4
  • Karl-Friedrich Becker
    • 5
  • Kuhn Uk Lee
    • 2
  • Han-Kwang Yang
    • 1
    • 2
    • 6
    Email author
  1. 1.Cancer Research InstituteSeoul National UniversitySeoulRepublic of Korea
  2. 2.Department of SurgerySeoul National University College of MedicineSeoulRepublic of Korea
  3. 3.Department of PathologySeoul National University College of MedicineSeoulRepublic of Korea
  4. 4.Central Animal LaboratoryNational Cancer Center Research InstituteTokyoJapan
  5. 5.Institut fuer PathologieKlinikum rechts der Isar, der Technischen UniversitaetMuenchenGermany
  6. 6.Department of Surgery and Cancer Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea

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