Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman; Molecular Medicine Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Indian J Med Res. 2022 Mar;155(3&4):335-346. doi: 10.4103/ijmr.IJMR_312_19.
The utilization of the monoclonal antibodies (mAbs) as therapeutic agents is one of the most favourable fields in immunotherapy. The immunogenicity of mAbs is one of the major parameters that may restrict their therapeutic and diagnostic applications. Rituximab, a chimeric mAb against CD20, is attached to the B-cell membrane-linked CD20 and is used to treat some B-cell-related malignancies, a number of autoantibody-mediated autoimmune disorders and improvement of graft survival. The risk of anti-rituximab antibody (ARA) development and ARA-related adverse events are low in rituximab-treated patients with lymphoma. No important association was reported between the ARA positivity and drug levels, and drug efficacy in rituximab-treated patients with lymphoma. The patients with autoimmune disorders exhibit greater risk of ARA development and ARA-related adverse events. In autoimmune diseases, ARA positivity may have no significant impact on either the drug level or its efficacy, (i.e.), it may reduce drug levels without influencing drug efficacy and, vice versa, or may reduce both drug level as well as its efficacy. The characterization of the parameters affecting the production of ARA can be used to design strategies to reduce the immunogenicity of mAb and promote its efficacy in humans. In this review, the host and therapeutic programme-related parameters affecting the development of the ARA have been discussed to suggest novel insights to reduce ARA-associated adverse events and enhance the drug efficacy.
单克隆抗体 (mAbs) 作为治疗剂的应用是免疫疗法中最有前途的领域之一。mAbs 的免疫原性是可能限制其治疗和诊断应用的主要参数之一。利妥昔单抗是一种针对 CD20 的嵌合 mAb，与 B 细胞膜上的 CD20 结合，用于治疗一些 B 细胞相关的恶性肿瘤、一些自身抗体介导的自身免疫性疾病和改善移植物存活。在接受利妥昔单抗治疗的淋巴瘤患者中，抗利妥昔单抗抗体 (ARA) 的发展和 ARA 相关不良事件的风险较低。在接受利妥昔单抗治疗的淋巴瘤患者中，未报告 ARA 阳性与药物水平和药物疗效之间存在重要关联。自身免疫性疾病患者发生 ARA 发展和 ARA 相关不良事件的风险更高。在自身免疫性疾病中，ARA 阳性可能对药物水平或其疗效没有显著影响，即可能降低药物水平而不影响药物疗效，反之亦然，或可能同时降低药物水平及其疗效。对影响 ARA 产生的参数进行特征描述可用于设计减少 mAb 免疫原性并提高其在人类中的疗效的策略。在这篇综述中，讨论了宿主和治疗方案相关参数对 ARA 发展的影响，以提出减少 ARA 相关不良事件和提高药物疗效的新见解。
