The epithelial glycoprotein 2 (EGP-2) promoter-driven epithelial-specific expression of EGP-2 in transgenic mice: a new model to study carcinoma-directed immunotherapy

Cancer Res. 2001 May 15;61(10):4105-11.


The human pancarcinoma-associated epithelial glycoprotein-2 (EGP-2), a M(r) 38,000 transmembrane antigen also known as 17-1A or Ep-CAM, is commonly used for targeted immunotherapy of carcinomas because it is strongly expressed by most carcinomas. EGP-2 is, however, also expressed in most normal epithelia. To evaluate anti-EGP-2-directed treatment-associated effects on tumors and on EGP-2-positive normal tissue, we generated EGP-2-expressing transgenic mice. A 55-kb DNA fragment consisting of the 14-kb genomic coding sequence of the human EGP-2 gene with approximately 10-kb-upstream and approximately 31-kb-downstream sequences was isolated and used to direct EGP-2 expression in an epithelium-specific manner. In the EGP-2 transgenic mice, EGP-2 appeared to be specifically expressed in all of those epithelial tissues that also express EGP-2 in humans, whereas all of the other tissues were negative. The specific in vivo localization of the i.v. administered anti-EGP-2 monoclonal antibody MOC31 was studied in EGP-2-positive and -negative tumors induced s.c. in this EGP-2 transgenic mouse model. Immunohistochemical analysis showed specific localization of MOC31 in the EGP-2-positive tumors but not in the EGP-2-negative tumors. No anti-EGP-2 monoclonal antibody localization was observed in any of the EGP-2-positive normal mouse tissues, which indicated a limited in vivo accessibility. In conclusion, an EGP-2 transgenic mouse model has been generated that expresses the EGP-2 antigen as in humans and, therefore, can serve as a model to evaluate the efficacy and safety of a variety of anti-EGP-2-based immunotherapeutic modalities in both tumors and normal tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / immunology*
  • Disease Models, Animal
  • Epithelial Cell Adhesion Molecule
  • Female
  • Humans
  • Immunotherapy / methods*
  • Male
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / therapy
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Promoter Regions, Genetic


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Epithelial Cell Adhesion Molecule