完全人源性单克隆抗体Panitumumab

Panitumumab:a fully human monoclonal antibody

panitumumab(ABX-EGF)是第一个完全人源性的针对表皮生长因子受体(EGFR)的单克隆抗体,现已进入临床试验用于治疗实体肿瘤。如同cetuximab(Er- bitux),它针对EGFR胞外配体结合域,其结果是阻断细胞内支配凋亡、增殖、分化的主要下游信号途径。它与EGFR有着很高的亲和力,无论是单独给药还是与其他化疗药物联合给药,均表现出有效性且被很好耐受,而且很少导致输液反应。已有可靠的、药代动力学资料证明,作为一种完全人源性的药剂,panitumumab不会导致体内形成任何针对其本身的抗体。其抗肿瘤活性在体外和体内试验中均得到证实,并且在大量恶性肿瘤模型中(特别是肺癌、肾癌和结直肠癌)均已观察到肿瘤生长受抑。与其他以EGFR途径为靶点的药物相似,皮疹为其主要副作用,且与给药剂量相关,皮疹的严重程度可能预测治疗效果;没有证据显示EGFR免疫组化染色是选择治疗对象的有效方法。目前尚未观察到不利的药物相互作用,亦未见其对同时使用的其他药物产生药代动力学上的影响。迄今为止,在既往经过治疗的结直肠癌患者中已经进行了若干Ⅰ期临床试验、两个Ⅱ期临床试验以及最近的一个Ⅲ期临床试验,尚有一个随机Ⅲ期临床试验正在研究panitu- mumab联合化疗在结直肠癌一线治疗中的作用。本文回顾总结了panitumumab在若干类型肿瘤中的临床前及临床研究的最新进展。

Panitumumab （ABX- EGF） is the first fully human monoclonal antibody targeting epidermal growth factor receptor （EGFR） to enter clinical trials for the treatment of solid tumors. Similiar to cetuximab （Erbitux） , panitumumab is against the extracellular ligand-binding domain of EGFR, resulting in the blockage of the downstream signaling pathways that are essential to the apoptosis, proliferation, and differentiation of cells. It is higly affinitive to EGFR and has been effective and well-tolerated both as monotherapy and in combination with other chemotherapeutic agents, with very few infusion reactions. As a fully human agent, panitumumab has not been demonstrated with the formation of any antibodies against itself by a very reliable pharmacokinetic profile. The anti-tumor activity of panitumumab has been tested in vitro and in vivo, and its inhibitory effect of tumor growth has been observed in many cancer models, particularly lung, kidney, and colorectal cancers. Rash is the main adverse event and is dose depend- ent, and the severity of the rash appears to be predictive of outcome. EGFR staining by immunohistochemistry has not been shown to be an effective method to select patients for treatment. No adverse pharmacokinetics among co-administered drugs was observed. Until recently, several phase Ⅰ trials, two phase Ⅱ trials, and one phase Ⅲ trial in pretreated colorectal cancer have been carried out. A randomized phase m trial investigating the role of panitumumab in the first-line treatment of colorectal cancer is also ongoing. This review summarizes recent progress in preclinical and clinical studies of panitumumab in several tumor types.