Antibodies are glycoproteins within the immunoglobulin (Ig) superfamily that serve a critical role in the functioning of the immune system. An antibody is shaped like a Y; the stem of the Y, which is known as the constant or Fc region, mediates the immune response by interacting with immune effector cells, such as macrophages. Created by identical B cells, monoclonal antibodies (mAbs) bind to a single epitope with a high degree of specificity. Since the 1980s, monoclonal antibodies have been utilized to help treat disease pathophysiology. Currently, there are more than 60 mAbs approved in the United States for treating a multitude of different diseases, and it is estimated that there are over 500 mAbs in the process of being clinically developed (Neurology Reviews, 2018).
Two general types of toxicities are associated with mAb therapy, which are target-related toxicity and non-specific toxicity. Target-related toxicity involves the mAb target and the biological consequences of that target being affected. As an example, certain oncology monoclonal antibodies target vascular endothelial growth factor (VEGF) to inhibit angiogenesis. A potential issue, however, can arise through the inhibition of VEGF signaling, which can reduce the growth of blood vessels in healthy tissues. Therefore, this could result in gastrointestinal perforations and complications with wound healing. In contrast, non-specific toxicity happens when the host immune system determines the therapeutic monoclonal antibody to be a foreign entity and therefore creates antibodies against the drug. This is known as immunogenicity. Complications that may result from immunogenicity include a loss of efficacy, hypersensitivity to the therapeutic mAb, injection site reactions, or severe allergic reactions. The risk of immunogenicity can be lowered by utilizing mAbs with lower proportions of non-human sequences. Additionally, this risk can be reduced by the removal of T-cell epitopes, formulation and purification improvements, and finding the proper dosing of the therapeutic mAb (Neurology Reviews, 2018).
Differences Between Monoclonal Antibodies and Small Molecules
Several differences exist between therapeutic monoclonal antibodies and small molecules. Compared to small molecules, mAbs have a high specificity, are less likely to induce drug-drug interactions, only minimally cross the blood brain barrier (BBB), have a much longer half life (days to weeks), and typically require less frequent dosing (monthly). Moreover, small molecules are generally metabolized via hepatic/renal mechanisms, while mAbs are metabolized by either the reticuloendothelial system and target-mediated disposition (Neurology Reviews, 2018).
To conclude, therapeutic monoclonal antibodies may be utilized to target different cell signaling pathways. Safety concerns with mAbs are associated with target-related or non-specific events. Today, therapeutic mAbs are being investigated and developed to help treat many different conditions, rendering them a promising form of future drug treatment (Neurology Reviews, 2018).
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The Science Behind Monoclonal Antibodies: What Neurologists Need to Know [PDF file]. (2018). Neurology Reviews,S1-S3. Retrieved May 20, 2018, from https://www.mdedge.com/sites/default/files/Document/April-2018/nr_amgen_novartis_april_supplement_4.4_final.pdf