In vitro and in vivo activity of MT201, a fully human monoclonal antibody for pancarcinoma treatment

In our study, a novel, fully human, recombinant monoclonal antibody of the IgG1 isotype, called MT201, was characterized for its binding properties, complement-dependent (CDC) and antibody-dependent cellular cytotoxicity (ADCC), as well as for its in vivo antitumor activity in a nude mouse model. MT201 was found to bind its target, the epithelial cell adhesion molecule (Ep-CAM; also called 17-1A antigen, KSA, EGP-2, GA733-2), with low affinity in a range similar to that of the clinically validated, murine monoclonal IgG2a antibody edrecolomab (Panorex(R)). MT201 exhibited Ep-CAM-specific CDC with a potency similar to that of edrecolomab. However, the efficacy of ADCC of MT201, as mediated by human immune effector cells, was by 2 orders of magnitude higher than that of edrecolomab. Addition of human serum reduced the ADCC of MT201 while it essentially abolished ADCC of edrecolomab within the concentration range tested. In a nude mouse xenograft model, growth of tumors derived from the human colon carcinoma line HT-29 was significantly and comparably suppressed by MT201 and edrecolomab. The fully human nature and the improved ADCC of MT201 with human effector cells will make MT201 a promising candidate for the clinical development of a novel pan-carcinoma antibody that is superior to edrecolomab.     

单克隆抗体类抗肿瘤药物的临床应用和进展

将化疗药物、放射性物质以及生物毒素等 与单克隆抗体偶联就得到单克隆类药物。由于抗原 抗体结合的特异性,这些偶联的药物被单克隆抗体 导向表达相应抗原的细胞并发挥抗肿瘤效应。单克 隆抗体类抗肿瘤药物有效地降低了传统肿瘤药物治 疗的不良反应,提高了治疗的精确性。