IDEC 10603--IDEC Y2B8 ADMINISTERED TO PATIENTS WITH B CELL LYMPHOMA

IDEC-Y2B8 （IDEC-103）是一种小鼠IgG1 kappa单克隆抗体，IDEC-C2B8 （IDEC-102）是一种嵌合的IgG1 kappa单克隆抗体，具有小鼠可变区和人恒定区。这两种抗体都能识别和特异性表达在正常B细胞和大多数恶性B细胞淋巴瘤上的CD20抗原。在食蟹猴中进行的高剂量安全性研究显示，这两种抗体均未发生不良临床事件，并且在实验室检查或组织病理学上均未发现显著异常。体外作用机制研究表明，IDEC-C2B8结合人补体并溶解淋巴样b细胞系。此外，它在抗体依赖性细胞毒性试验中具有显著的活性。正如预测的那样，这些抗体的生物学效应表现为外周血、淋巴结和骨髓中的b细胞耗竭。在单独的研究中，在7个q.o.d.剂量的IDEC-2B8后的几周，以及在4个星期剂量的IDEC-2B8后的三周，观察到骨髓中B细胞的显著减少。外周血B细胞的恢复（至基线的75%）通常分别发生在末次给药后38天和60天内。

IDEC-Y2B8 (IDEC-103) is a murine IgG1 kappa monoclonal antibody and IDEC-C2B8 (IDEC-102) is a chimeric igG1 kappa monoclonal antibody, with mouse variable and human constant regions. Both antibodies recognize and show specificity for the CD20 antigen expressed on normal B cells and most malignant B-cell lymphomas. High-dose safety studies in cynomolgus monkeys have revealed no adverse clinical events with either antibody, and there were no significant abnormalities on laboratory tests or on histopathology. In vitro mechanism of action studies have demonstrated that IDEC-C2B8 binds human complement and lyses lymphoid B-cell lines. Additionally, it has significant activity in assays for antibody-dependent cellular cytotoxicity. As predicted, the biologic effect of these antibodies is manifested by B-cell depletion in peripheral blood, lymph nodes and bone marrow. In separate studies, several weeks after seven q.o.d. doses of IDEC-2B8, and three weeks after four weekly doses of IDEC-C2B8, a significant decrease of B cells in bone marrow was observed. Recovery of the B cells in the peripheral blood (to >75% of baseline) usually occurred within 38 days and 60 days following the last dose of IDEC-2B8 and IDEC-C2B8, respectively.