Foon Kenneth A, Yang Xiao-Dong, Weiner Louis M, Belldegrun Arie S, Figlin Robert A, Crawford Jeffrey, Rowinsky Eric K, Dutcher Janice P, Vogelzang Nicholas J, Gollub Jared, Thompson John A, Schwartz Garry, Bukowski Ronald M, Roskos Lorin K, Schwab Gisela M
Abgenix, Inc., Fremont, CA, USA.
Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):984-90. doi: 10.1016/j.ijrobp.2003.09.098.
The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, with an extracellular ligand-binding domain and intracellular tyrosine kinase domain. Ligand binding induces EGFR dimerization and autophosphorylation on several tyrosine residues in the intracellular domain, leading to mitogenic signal transduction. EGFR overexpression correlates with a poor prognosis and is often associated with malignant transformation in a variety of epithelial cancers. ABX-EGF is a high-affinity (dissociation constant K(D) = 5 x 10(-11) M) fully human IgG2 monoclonal antibody against human EGFR. ABX-EGF binds EGFR and blocks receptor binding of EGF and transforming growth factor-alpha, inhibiting EGFR tyrosine phosphorylation and tumor cell activation. ABX-EGF prevents tumor formation and eradicates large, established A431 tumors in xenograft models. Tumor growth inhibition occurs at relatively low doses, without concomitant chemotherapy or radiotherapy. When combined with chemotherapeutic agents, ABX-EGF has resulted in additive antitumor activity. A Phase I clinical trial has demonstrated activity in several tumor types, and the results from a Phase II trial for renal cell cancer also showed modest activity. Therapy was generally well tolerated without statistically significant adverse events. Monoclonal antibody blockade of EGFR represents a new and exciting direction in cancer therapy.
表皮生长因子受体（EGFR）是一种跨膜糖蛋白，具有细胞外配体结合结构域和细胞内酪氨酸激酶结构域。配体结合诱导EGFR二聚化并使其细胞内结构域中的多个酪氨酸残基发生自身磷酸化，从而导致有丝分裂信号转导。EGFR的过表达与预后不良相关，并且在多种上皮癌中常与恶性转化有关。ABX-EGF是一种针对人EGFR的高亲和力（解离常数K(D)=5×10(-11)M）的全人IgG2单克隆抗体。ABX-EGF与EGFR结合并阻断EGF和转化生长因子-α与受体的结合，抑制EGFR酪氨酸磷酸化和肿瘤细胞活化。在异种移植模型中，ABX-EGF可预防肿瘤形成并根除已形成的大的A431肿瘤。在相对较低剂量下即可发生肿瘤生长抑制，无需同时进行化疗或放疗。当与化疗药物联合使用时，ABX-EGF具有相加的抗肿瘤活性。一项I期临床试验已证明其在几种肿瘤类型中具有活性，一项肾细胞癌II期试验的结果也显示出一定活性。该治疗总体耐受性良好，无统计学意义的不良事件。对EGFR的单克隆抗体阻断代表了癌症治疗中一个新的、令人兴奋的方向。
