In Vivo Properties of Three Human HER2/neu-Expressing Murine Cell Lines in Immunocompetent Mice
Abstract:Background and purpose: Expression of the HER2/neu proto-oncogene, a receptor-like transmembrane protein expressed at low levels on some normal cells, is markedly increased in a subset of human breast, colon, lung, and ovarian cancers. A humanized HER2/neu antibody has been tested as a therapeutic agent in several clinical trials, with promising results. We have developed a family of anti-HER2/neu fusion proteins. To evaluate the immunologic efficacy of these proteins, it is critical that tumors expressing the target antigen can grow in immunologically intact mice.
Method: To produce murine tumors expressing human HER2/neu on the surface, CT26, MC38, and EL4 murine cell lines were transduced by use of a retroviral construct containing the cDNA encoding the human HER2/neu gene.
Results: Histologic features and kinetics of tumor growth in subcutaneous space of the human HER2/neu-expressing cells were similar to those of the respective parental cell lines. Intravenous inoculation with these cells induced disseminated malignant disease. Flow cytometric and immmunohistochemical analyses of freshly isolated tumors revealed in vivo expression of human HER2/neu. Secretion of antigen was not detected by use of an ELISA.
Conclusion: Although an antibody response against the human HER2/neu antigen was observed, this response does not affect the growth rate of the HER2/neu-expressing cells. These murine models may be useful tools for evaluation of anti-cancer therapeutic approaches that target human HER2/neu.
Document Type: Research Article
Affiliations: 1: Departments of Microbiology and Molecular Genetics, Microbiology and Immunology and The Molecular Biology Institute, Los Angeles, California 2: Department of Medicine, Microbiology and Immunology, Cancer Center, University of Rochester, Rochester, New York 3: Institute of Environment and Life Science, The Hallym Academy of Sciences, Hallym University, Chunchon, Kangwon-Do, Korea 4: Department of Neurobiology and the Brain Research Institute, University of California, Los Angeles, California 5: Department of Microbiology and Molecular Genetics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095-1489
Publication date: April 1, 1999
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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