Newsome Barrett W, Ernstoff Marc S
Section of Hematology/Oncology, Dartmouth Medical Center, Lebanon, NH 03756, USA.
Br J Clin Pharmacol. 2008 Jul;66(1):6-19. doi: 10.1111/j.1365-2125.2008.03187.x. Epub 2008 May 22.
Monoclonal antibodies (Mabs) are proteins in the immunoglobulin family that bind to specific protein epitope targets on cancer and stromal cells, allowing them to be successfully exploited as therapeutic agents. The prototype Mabs were produced from fusion of mouse B lymphocytes and mouse myeloma cells and were entirely murine in sequence. Subsequent advances in technology have allowed for humanized Mabs, which have different pharmacokinetic properties than murine Mabs in humans. Mabs antitumour activity is mediated through direct interaction with specific target molecules, deployment of immune cytotoxic pathways, or through chaperoning cytotoxic agents to tumour. Mabs are typically administered intravenously, are generally well tolerated and can have powerful anticancer activity. Humanized Mabs have a t(1/2) in human sera of 2-3 weeks, which determines the frequency of administration. At present, nine clinically approved Mabs are used in the treatment of human cancer, and many others are in clinical trials. We discuss the pharmacology, clinical indications, and toxicity of the currently available anticancer Mabs in this review.
单克隆抗体（Mabs）是免疫球蛋白家族中的蛋白质，可与癌症和基质细胞上的特定蛋白质表位靶点结合，从而使其能够成功用作治疗药物。原型单克隆抗体由小鼠B淋巴细胞和小鼠骨髓瘤细胞融合产生，其序列完全是鼠源的。随后的技术进步使得人源化单克隆抗体得以出现，其人源化单克隆抗体在人体内具有与鼠源单克隆抗体不同的药代动力学特性。单克隆抗体的抗肿瘤活性是通过与特定靶分子直接相互作用、免疫细胞毒性途径的激活或通过将细胞毒性药物输送至肿瘤来介导的。单克隆抗体通常通过静脉给药，一般耐受性良好，并且可以具有强大的抗癌活性。人源化单克隆抗体在人血清中的半衰期为2至3周，这决定了给药频率。目前，有九种临床批准的单克隆抗体用于治疗人类癌症，还有许多其他单克隆抗体正在进行临床试验。在本综述中，我们讨论了目前可用的抗癌单克隆抗体的药理学、临床适应症和毒性。
