Abstract
Antibodies against the receptor for epidemal growth factor (EGF-R) have long been expected to turn out to be anticancer agents (Mendelsohn et al. 1988). The overexpression of EGF-R is the most constant pathological cell biological feature of human malignant gliomas of the astrocytic lineage (Bigner et al. 1988; Libermann et al. 1985). Such overexpression may be due to gene amplification of the EGF-R gene on chromosome 7 (Bigner and Vogelstein 1990) but may also be present in the absence of gene amplification due to other mechanisms (Chaffanet et al. 1992). An antibody against the extracellular domain of the EGF-R has been generated several years ago, called MAb 425 (Rodeck et al. 1987) and has been developed into a therapeutic compound (EMD 55900). The effects of this antibody as well as others on cell proliferation have been studied in cell culture and in xenotransplants, with contradicting results (Aboud-Pirak et al. 1988; Bigner et al.1988; Rodeck et al. 1987; Werner et al. 1988). It was thought that the antibody might be effective by inhibiting the autocrine self-stiumulation of tumor cells which is afforded by the concomitant secretion of transforming growth factor-α (TGF-α), a homologue to EGF and overexpression of EGF-R (Di Marco et al. 1989). It has yet to be confirmed that this mechanism contributes substantially to the sustained cell proliferation seen in brain tumors. For this interaction to be at all relevant, it has been shown that certain quantitative requirements need to be met (Di Marco et al. 1989). There is only scant clinical evidence that the expression of EGF-R in gliomas due to gene amplification is associated with worse prognosis (Hurtt et al. 1992), and in cell lines it has been shown that despite the presence of the constituents of the autocrine loop for EGF/TGF-α there is little dependence of the cells on this loop for autostimulation of proliferation (Westphal et al., 1993).
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© 1994 Springer-Verlag Berlin Heidelberg
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Westphal, M. et al. (1994). Epidermal Growth Factor Receptor Expression in Human Malignant Glioma: In Vitro and In Vivo Effects of Application of Monoclonal Antibodies to the Epidermal Growth Factor Receptor. In: Wiestler, O.D., Schlegel, U., Schramm, J. (eds) Molecular Neuro-oncology and Its Impact on the Clinical Management of Brain Tumors. Recent Results in Cancer Research, vol 135. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85039-4_17
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DOI: https://doi.org/10.1007/978-3-642-85039-4_17
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