Contemporary Monoclonal Antibody Utilization in Glomerular Diseases

Abstract

Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, reduced number of drug-drug interactions, and low toxicity, which make them a prime example of personalized medicine. In this review article, we provide an overview of the taxonomy, pharmacology, and therapeutic applications of MAbs in glomerular diseases. We searched the literature through PubMed using the following search terms: monoclonal antibodies, glomerular diseases, pharmacokinetics, pharmacodynamics, immunoglobulin, murine, chimeric,humanized, and fully human, and limited our search to years 2018-2023. We selected peer-reviewed journal articles with an evidence-based approach, prioritizing randomized control trials in specific glomerular diseases, if available. Advances in the MAb field have resulted in a significant paradigm shift in targeted treatment of immune-mediated glomerular diseases, and multiple randomized control trials are currently being conducted. Increased recognition is critical to expand their use in experimental research and personalized medicine.

Figure 1

The structure of a chimeric monoclonal antibody. The variable light (VL) and variable heavy (VH) chains are the regions that recognize and bind to the antigen. The constant light (CL) and constant heavy (CH) regions provide structural stability and determine the antibody's class (eg, IgG, IgM, and IgE). The fragment antigen-binding (Fab) region is composed of the VL and VH domains and is responsible for antigen recognition and binding. The fragment crystallizable (Fc) region is composed of the CH domains and is responsible for effector functions, such as complement activation and binding to Fc receptors.

Figure 2

The mechanism of the action of rituximab. Rituximab is a chimeric monoclonal antibody that specifically binds to the CD20 antigen on B cells, after which CD20 triggers a series of immune responses that ultimately lead to the destruction of B cells, such as antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and induction of apoptosis (programmed cell death).