Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo de Degollado, MEX, Mexico.
Dirección Médica, Probiomed S.A. de C.V., Avenida Ejército Nacional No. 499, Colonia Granada, Delegación Miguel Hidalgo, 11520 México, DF, Mexico.
J Immunol Res. 2015;2015:910763. doi: 10.1155/2015/910763. Epub 2015 Apr 20.
Rituximab is a chimeric monoclonal antibody employed for the treatment of CD20-positive B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis. It binds specifically to the CD20 antigen expressed on pre-B and consequently on mature B-lymphocytes of both normal and malignant cells, inhibiting their proliferation through apoptosis, CDC, and ADCC mechanisms. The immunomodulatory activity of rituximab is closely related to critical quality attributes that characterize its chemical composition and spatial configuration, which determine the recognition of CD20 and the binding to receptors or factors involved in its effector functions, while regulating the potential immunogenic response. Herein, we present a physicochemical and biological characterization followed by a pharmacodynamics and immunogenicity study to demonstrate comparability between two products containing rituximab. The physicochemical and biological characterization revealed that both products fit within the same response intervals exhibiting the same degree of variability. With regard to clinical response, both products depleted CD20+ B-cells until posttreatment recovery and no meaningful differences were found in their pharmacodynamic profiles. The evaluation of anti-chimeric antibodies did not show differential immunogenicity among products. Overall, these data confirm that similarity of critical quality attributes results in a comparable immunomodulatory activity.
利妥昔单抗是一种嵌合型单克隆抗体，用于治疗 CD20 阳性 B 细胞非霍奇金淋巴瘤、慢性淋巴细胞白血病、类风湿关节炎、肉芽肿性多血管炎和显微镜下多血管炎。它特异性地结合到表达在正常和恶性细胞前 B 细胞和成熟 B 淋巴细胞上的 CD20 抗原，通过细胞凋亡、CDC 和 ADCC 机制抑制其增殖。利妥昔单抗的免疫调节活性与其化学组成和空间构象的关键质量属性密切相关，这些属性决定了其对 CD20 的识别以及与参与其效应功能的受体或因子的结合，同时调节潜在的免疫原性反应。在此，我们进行了理化特性和生物学特性分析，随后进行了药效学和免疫原性研究，以证明两种含有利妥昔单抗的产品之间的可比性。理化特性和生物学特性分析表明，两种产品均处于相同的反应区间内，具有相同的变异性程度。就临床反应而言，两种产品均耗尽了 CD20+B 细胞，直至治疗后恢复，并且在药效学特征方面没有发现有意义的差异。抗嵌合抗体的评估并未显示产品之间存在免疫原性差异。总体而言，这些数据证实了关键质量属性的相似性可导致相当的免疫调节活性。
