Govindan Serengulam V, Goldenberg David M
Immunomedics, Inc., Morris Plains, NJ, USA.
ScientificWorldJournal. 2010 Oct 12;10:2070-89. doi: 10.1100/tsw.2010.191.
Targeting of radiation, drugs, and protein toxins to cancers selectively with monoclonal antibodies (MAbs) has been a topic of considerable interest and an area of continued development. Radioimmunotherapy (RAIT) of lymphoma using directly labeled MAbs is of current interest after approval of two radiolabeled anti-CD20 MAbs, as illustrated with the near 100% overall response rate obtained in a recent clinical trial using an investigational radiolabeled anti-CD22 MAb, 90Y-epratuzumab. The advantage of pretargeted RAIT over directly labeled MAbs is continuing to be validated in preclinical models of lymphoma and solid tumors. Importantly, the advantages of combining RAIT with radiation sensitizers, with immunotherapy, or a drug conjugate targeting a different antigen are being studied clinically and preclinically. The area of drug-conjugated antibodies is progressing with encouraging data published for the trastuzumab-DM1 conjugate in a phase I clinical trial in HER2-positive breast cancer. The Dock-and-Lock platform technology has contributed to the design and the evaluation of complex antibody-cytokine and antibody-toxin conjugates. This review describes the advances made in these areas, with illustrations taken from advances made in the authors' institutions.
利用单克隆抗体（MAb）将辐射、药物和蛋白质毒素选择性地靶向癌症一直是备受关注的话题，也是一个持续发展的领域。在两种放射性标记的抗CD20单克隆抗体获批后，使用直接标记的单克隆抗体进行淋巴瘤的放射免疫疗法（RAIT）成为当前的研究热点，如最近一项使用研究性放射性标记抗CD22单克隆抗体90Y-依帕珠单抗的临床试验中获得了近100%的总缓解率所示。预靶向RAIT相对于直接标记单克隆抗体的优势在淋巴瘤和实体瘤的临床前模型中不断得到验证。重要的是，正在临床和临床前研究将RAIT与辐射增敏剂、免疫疗法或靶向不同抗原的药物偶联物相结合的优势。药物偶联抗体领域正在取得进展，在HER2阳性乳腺癌的I期临床试验中，曲妥珠单抗-DM1偶联物已公布了令人鼓舞的数据。对接锁定平台技术有助于设计和评估复杂的抗体-细胞因子和抗体-毒素偶联物。本综述描述了这些领域取得的进展，并举例说明了作者所在机构取得的进展。
