The University of Texas, MD Anderson Cancer Center, Department of Lymphoma/Myeloma, Houston, Texas 77030, USA.
Expert Opin Investig Drugs. 2010 Jan;19(1):141-9. doi: 10.1517/13543780903463854.
Milatuzumab is a new immunotherapeutic agent targeting CD74, a membrane protein preferentially expressed in hematopoietic cancers and some solid tumors. Broad expression and fast internalization makes CD74 an ideal target for cancer therapy. We reviewed published articles about CD74 and milatuzumab. We present a comprehensive review of CD74 functions and provide explanation of milatuzumab antitumor effects. This review describes CD74 protein biology with the emphasis on the role of CD74 in tumor survival and its new role in regulation of the Fas death receptor. The development of CD74 targeting therapies to induce tumor regression and cancer cell apoptosis is described and results of clinical trials are discussed. Milatuzumab shows selective binding and rapid internalization into CD74-positive cancer cells. Milatuzumab with and without conjugated toxins synergizes with other chemotherapeutic agents and elicits significant antitumor effects in mice. In a Phase I trial, milatuzumab showed no severe adverse effects in patients with relapsed/refractory multiple myeloma and it stabilized the disease in some patients for up to 12 weeks. Ongoing trials testing different treatment schedules of milatuzumab in chronic lymphocytic leukemia, non-Hodgkin's lymphoma and multiple myeloma indicate that milatuzumab shows no severe adverse effects in humans.
美拉珠单抗是一种新型免疫治疗药物，针对 CD74，一种优先在造血系统癌症和一些实体瘤中表达的膜蛋白。广泛的表达和快速内化使 CD74 成为癌症治疗的理想靶点。我们回顾了有关 CD74 和美拉珠单抗的已发表文章。我们全面回顾了 CD74 的功能，并解释了美拉珠单抗的抗肿瘤作用。本文描述了 CD74 蛋白生物学，重点介绍了 CD74 在肿瘤存活中的作用及其在 Fas 死亡受体调节中的新作用。描述了针对 CD74 的靶向治疗以诱导肿瘤消退和癌细胞凋亡的发展，并讨论了临床试验结果。美拉珠单抗显示出对 CD74 阳性癌细胞的选择性结合和快速内化。美拉珠单抗与缀合毒素联合使用或不联合使用，与其他化疗药物协同作用，在小鼠中产生显著的抗肿瘤作用。在一项 I 期试验中，美拉珠单抗在复发性/难治性多发性骨髓瘤患者中未显示出严重的不良反应，并且在一些患者中可使疾病稳定长达 12 周。正在进行的临床试验测试了美拉珠单抗在慢性淋巴细胞白血病、非霍奇金淋巴瘤和多发性骨髓瘤中的不同治疗方案，表明美拉珠单抗在人类中未显示出严重的不良反应。
