Binding of EGF peptide and EGF receptor antibodies and its fragments in different tumor models.
Binding of epidermal growth factor (EGF) to the EGF receptor is known to trigger a number of biological responses in the target cells including EGF receptor phosphorylation and stimulation of DNA synthesis leading to cell proliferation. Agents that bind to the EGF receptors could have a significant role in the therapy of tumors that express increased numbers of receptors by blocking the stimulatory effect of EGF. Different monoclonal antibodies (MAbs) directed to the EGF receptor have been generated that inhibit EGF binding and do not induce activation of the receptor tyrosine kinase. When there is sufficient uptake these antibodies can be used for immunotherapy and, after labeling with an appropriate radionuclide, also for radioimmunotherapy. For evaluation of a ligand as a therapeutic agent, it is necessary to investigate its binding characteristics in tumor cells and experimental tumors in vivo. Because the effectiveness of the antitumor activity of the MAb is dependent upon the amount of receptors in the tissue and the penetration of the MAb into the tissue, the receptor density, biokinetics, and tumor distribution of the MAb or its fragments were evaluated in different tumor models. The results of the experimental studies with tumor cell spheroids and different xenotransplanted human tumors have shown that the uptake and distribution in the tumor tissue is dependent on the molecular weight of the ligand. The correlation between the uptake of the substances and the receptor density is an indication for a noninvasive scintigraphic characterization of human tumors using radiolabeled compounds with specific binding to the tumor receptor and for selection of an optimal therapeutic regimen or radionuclide targeting of the tumor.
Senekowitsch-Schmidtke
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Nuklearmedizinische Klinik und Poliklinik der Technischen Universität, Technische Universität München, Germany.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division; D004815:Epidermal Growth Factor / Q000276:immunology* / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D066246:ErbB Receptors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism; D007457:Iodine Radioisotopes; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D016719:Radioimmunodetection; D018874:Spheroids, Cellular / Q000276:immunology / Q000378:metabolism; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D066246:ErbB Receptors