Division of Hematology/Oncology, Mayo Clinic, Scottsdale, AZ, USA.
Expert Opin Biol Ther. 2010 Aug;10(8):1251-8. doi: 10.1517/14712598.2010.498418.
More than 65,000 cases of non-Hodgkin's lymphoma are estimated to have been diagnosed in 2009; the majority are of B-cell lineage, and diffuse large cell lymphoma and follicular together account for nearly half of cases. Despite advances in treatment, most patients are not cured.
The antigen CD22 is a transmembrane glycoprotein found on mature B-cells, and on up to 90% of B-cell malignancies. Inotuzumab ozogamicin (CMC-544) is a humanized anti-CD22 monoclonal antibody conjugated with calicheamicin. Preclinical data indicate activity against B-cell tumors, and early results from clinical trials indicate activity against B-cell lymphomas including follicular lymphoma and diffuse large cell lymphoma. This paper reviews the design, pharmacokinetic and pharmacodynamic characteristics, and preclinical and clinical experience of this promising novel targeted therapy, with data derived from abstracts and published reports from 2002 to the present.
This review will serve as an introduction to and overview of inotuzumab ozogamicin, and describe the rationale guiding advances in development.
The data thus far confirm the tolerability and clinical activity of inotuzumab ozogamicin in B-cell malignancies, and further investigation as a single agent as well as in combination therapy is warranted.
估计 2009 年诊断出超过 65000 例非霍奇金淋巴瘤; 大多数是 B 细胞谱系,弥漫性大细胞淋巴瘤和滤泡性淋巴瘤一起占近一半的病例。尽管治疗取得了进展,但大多数患者仍未治愈。
抗原 CD22 是一种在成熟 B 细胞上发现的跨膜糖蛋白,在多达 90%的 B 细胞恶性肿瘤上。Inotuzumab ozogamicin (CMC-544) 是一种人源化抗 CD22 单克隆抗体,与 calicheamicin 结合。临床前数据表明对 B 细胞肿瘤具有活性,早期临床试验结果表明对包括滤泡性淋巴瘤和弥漫性大细胞淋巴瘤在内的 B 细胞淋巴瘤具有活性。本文综述了这种有前途的新型靶向治疗的设计、药代动力学和药效学特征、临床前和临床经验,并从 2002 年至今的摘要和已发表的报告中获取了数据。
这篇综述将作为 inotuzumab ozogamicin 的介绍和概述,并描述指导其开发的基本原理。
迄今为止的数据证实了 inotuzumab ozogamicin 在 B 细胞恶性肿瘤中的耐受性和临床活性,进一步作为单一药物以及联合治疗的研究是合理的。