Department of Medical Science, Surgery and Neuroscience, Hematology, University of Siena, Siena, Italy.
Hum Vaccin Immunother. 2022 Nov 30;18(5):2052658. doi: 10.1080/21645515.2022.2052658. Epub 2022 Apr 11.
CD38 is a transmembrane glycoprotein with ectoenzymatic activity and is highly and uniformly expressed on multiple myeloma (MM) cells. CD38 is expressed also at relatively low levels on normal lymphoid and myeloid cells, and in some tissues of non-hematopoietic origin. The specificity of this target has increased interest in new drugs and triggered the development of the CD38 monoclonal antibodies Daratumumab (fully human) and Isatuximab (chimeric). CD38 antibodies have pleiotropic mechanisms of action including Fc-dependent immune effector mechanisms, direct apoptotic activity, and immunomodulatory effects by the elimination of CD38+ immune-suppressor cells. Monoclonal antibody-based therapy has revolutionized MM therapy in the latest years increasing depth of response. This product review will focus on anti-CD38 monoclonal antibodies Daratumumab and Isatuximab efficacy, safety, pharmacokinetic and pharmacodynamic data from clinical trials.
CD38 是一种跨膜糖蛋白,具有外切酶活性,在多发性骨髓瘤(MM)细胞上高度且均匀表达。CD38 也在正常淋巴样和髓样细胞以及非造血组织的某些部位以相对较低的水平表达。该靶点的特异性增加了对新药的兴趣,并促使开发了 CD38 单克隆抗体 Daratumumab(全人源)和 Isatuximab(嵌合)。CD38 抗体具有多种作用机制,包括 Fc 依赖性免疫效应机制、直接凋亡活性以及通过消除 CD38+免疫抑制细胞的免疫调节作用。基于单克隆抗体的治疗在近年来彻底改变了 MM 治疗,增加了反应深度。本产品评价将重点关注抗 CD38 单克隆抗体 Daratumumab 和 Isatuximab 的疗效、安全性、药代动力学和来自临床试验的药效学数据。