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

IDEC 10603--IDEC Y2B8 用于 B 细胞淋巴瘤患者

• 批准号: 6114067
• 负责人: Leo I. Gordon
• 金额: $ 2.05万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6114067
• 关键词: B lymphocyte; CD antigens; clinical research; clinical trial phase I; human subject; immunotherapy; monoclonal antibody

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.

IDEC-Y2B8 (IDEC-103) 是一种鼠 IgG1 kappa 单克隆抗体，IDEC-C2B8 (IDEC-102) 是一种嵌合 igG1 kappa 单克隆抗体，具有小鼠可变区和人恒定区。 两种抗体均能识别正常 B 细胞和大多数恶性 B 细胞淋巴瘤上表达的 CD20 抗原并表现出特异性。 在食蟹猴中进行的高剂量安全性研究表明，这两种抗体都没有出现不良临床事件，实验室测试或组织病理学也没有出现明显异常。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，它在抗体依赖性细胞毒性测定中具有显着的活性。 正如预测的那样，这些抗体的生物学效应通过外周血、淋巴结和骨髓中 B 细胞的消耗来体现。 在单独的研究中，每周七次后几周。每周剂量的 IDEC-2B8 和四周剂量的 IDEC-C2B8 后三周，观察到骨髓中 B 细胞显着减少。 外周血中 B 细胞的恢复（恢复至基线的 75% 以上）通常分别发生在 IDEC-2B8 和 IDEC-C2B8 最后一剂后的 38 天内和 60 天内。