Lynch David H, Yang Xiao-Dong
Department of Cancer Biology, Immunex Corporation, Seattle, WA 98101, USA.
Semin Oncol. 2002 Feb;29(1 Suppl 4):47-50. doi: 10.1053/sonc.2002.31522.
Overexpression of the epidermal growth factor receptor (EGFR) has been observed in a wide variety of human cancers and is associated with a poor clinical prognosis. In many cases, growth of the tumor cells is dependent on EGFR-mediated signals, because inhibition of binding of factors to the EGFR leads to cell death. Using XenoMouse technology, a fully human EGFR-specific monoclonal antibody, ABX-EGF, with high affinity (5 x 10(-11) mol/L) has been generated. ABX-EGF blocks binding of both epidermal growth factor and transforming growth factor alpha to the EGFR, inhibits tyrosine phosphorylation of the EGFR, and inhibits cellular proliferation. In vivo, ABX-EGF not only blocks formation of human epidermoid carcinoma A431 xenografts in athymic mice, but also mediates therapeutic elimination of established tumors and acts cooperatively with chemotherapeutics in mediating tumor regression. These observations provide a strong basis for the development of ABX-EGF as a therapeutic agent for human solid tumors that overexpress EGFR.
在多种人类癌症中均观察到表皮生长因子受体（EGFR）的过表达，且其与不良临床预后相关。在许多情况下，肿瘤细胞的生长依赖于EGFR介导的信号，因为抑制因子与EGFR的结合会导致细胞死亡。利用人源化小鼠技术，已产生了一种具有高亲和力（5×10⁻¹¹ mol/L）的完全人源化EGFR特异性单克隆抗体ABX - EGF。ABX - EGF可阻断表皮生长因子和转化生长因子α与EGFR的结合，抑制EGFR的酪氨酸磷酸化，并抑制细胞增殖。在体内，ABX - EGF不仅可阻断无胸腺小鼠中人表皮样癌A431异种移植瘤的形成，还可介导对已形成肿瘤的治疗性清除，并在介导肿瘤消退方面与化疗药物协同作用。这些观察结果为将ABX - EGF开发为治疗过表达EGFR的人类实体瘤的治疗药物提供了有力依据。
