IDEC 106-03--PHASE I/II CLINICAL TRIAL TO EVALUATE IDEC-Y2B8

IDEC-Y2B8(IDEC-103)是一种小鼠IgG1 kappa单抗。 C2B8(IDEC-102)是一种嵌合的IgG1 kappa单抗，与小鼠 可变区和人类恒定区。这两种抗体都能识别并显示 CD20抗原在正常B细胞和MOST细胞上表达的特异性 恶性B细胞淋巴瘤。食蟹大剂量安全性研究 猴子使用这两种抗体都没有表现出不良的临床事件， 实验室检查或其他检查均未发现明显异常。 组织病理学。体外作用机制研究表明 IDEC-C2B8结合人类补体并裂解淋巴B细胞系。 此外，它在抗体检测中具有显著的活性- 依赖的细胞细胞毒性。正如预测的那样，病毒的生物效应 这些抗体表现为外周血液中B细胞的耗尽， 淋巴和骨髓。在单独的研究中，几周后 七个Q.O.D.IDEC-Y2B8剂量，每周四次剂量后3周 IDEC-C2B8后，骨髓中B细胞明显减少。 外周血中B细胞的恢复(恢复至基线的75%) 通常发生在最后一剂的38天和60天内 IDEC-Y2B8和IDEC-C2B8。

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-Y2B8, and 3 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-Y2B8 and IDEC-C2B8, respectively.