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

IDEC-Y2 B8（IDEC-103）是一种鼠IgG 1 κ单克隆抗体，IDEC- C2 B8（IDEC-102）是一种嵌合IgG 1 κ单克隆抗体， 可变区和人恒定区。 两种抗体都能识别并显示 对正常B细胞上表达的CD 20抗原和大多数 恶性B细胞淋巴瘤 食蟹猴高剂量安全性研究 猴子没有发现任何一种抗体的不良临床事件， 实验室检查或 组织病理学 体外作用机制研究表明， IDEC-C2 B8结合人补体并裂解淋巴B细胞系。 此外，它在抗体测定中具有显著的活性， 依赖细胞毒性。 正如预测的那样， 这些抗体表现为外周血中的B细胞耗竭， 淋巴结和骨髓在不同的研究中，几周后， 每天七次。IDEC-Y2 B8给药，每周4次IDEC-Y2 B8给药后3周 IDEC-C2 B8，观察到骨髓中B细胞显著减少。 外周血中B细胞的回收率（>基线的75%） 通常发生在末次给药后38天和60天内 IDEC-Y2 B8和IDEC-C2 B8。

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.