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

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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.

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Abbreviations

mAb:

Monoclonal antibody

DGC:

Diffuse-type gastric cancer

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Acknowledgment

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

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Authors and Affiliations

  1. Cancer Research Institute, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea

    Hyuk-Joon Lee, Keun Hur, Woo Ho Kim & Han-Kwang Yang

  2. Department of Surgery, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea

    Hyuk-Joon Lee, Kuhn Uk Lee & Han-Kwang Yang

  3. Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea

    Hye Seung Lee & Woo Ho Kim

  4. Central Animal Laboratory, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, chuo-ku, Tokyo, 104-0045, Japan

    Kazuyoshi Yanagihara

  5. Institut fuer Pathologie, Klinikum rechts der Isar, der Technischen Universitaet, Trogerstrasse 18/III.Stock/R3.16, 81675, Muenchen, Germany

    Karl-Friedrich Becker

  6. Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Republic of Korea

    Han-Kwang Yang

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  1. Hyuk-Joon Lee
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  2. Hye Seung Lee
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Correspondence to Han-Kwang Yang.

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Lee, HJ., Lee, H.S., Hur, K. et al. Tumor specificity and in vivo targeting of an antibody against exon 9 deleted E-cadherin in gastric cancer. J Cancer Res Clin Oncol 133, 987–994 (2007). https://doi.org/10.1007/s00432-007-0246-5

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  • DOI: https://doi.org/10.1007/s00432-007-0246-5

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