What is an ADA Assay?
Large drug molecules, such as biologics, can elicit an immunogenic response in the body. The body’s immune system recognizes these molecules as foreign bodies and triggers an immune response, producing antibodies specific to the drug molecules. The B-cells of the immune system secrete antibodies, which are glycoproteins belonging to the superfamily of immunoglobulins. These immunoglobulins can lower the efficacy of the drug and lead to life-threatening adverse events and treatment failure. Hence, it is crucial to determine the immunogenicity of large drug molecules.
Anti-drug antibody (ADA) assay is a biochemical method for detecting antibodies that the immune system produces when it encounters protein, antibody therapeutics, and large drug molecules. ADA Assays involve a screening assay to detect ADA, followed by a confirmation assay to verify the specificity of the ADA detected. Assays such as characterization, affinity, and functional assays may also be incorporated into the ADA assay protocol. Additionally, NAb assays help to assess whether neutralizing antibodies (a subset of ADAs) detected in the sample can neutralize the biological activity of the drug molecule. The ADA and NAb assays help in the immunogenicity testing of large drug molecules, thereby determining their safety and efficacy. Thus, ADA assays are an indispensable tool in the drug development process.
What is Monoclonal Therapy?
Monoclonal antibodies are γ-immunoglobulins (IgG) that contain hypervariable regions of heavy and light chains connecting to form the antigen-binding site or the Fab domain, while the two constant domains function as the Fc (fragment crystallizable) domain. The Fc domain is responsible for the effector function of IgG.
Monoclonal therapy, also commonly referred to as monoclonal antibody therapy, is a biological treatment that utilizes laboratory-made antibodies to target and treat specific diseases. These are synthetic antibodies designed to mimic the intrinsically produced antibodies in the body by the immune system. These antibodies can specifically bind to antigens associated with the target disease. This makes them beneficial in treating autoimmune disorders, certain cancers, metabolic and infectious diseases, as well as other conditions that are difficult to treat using traditional therapeutics. Consequently, therapeutic antibodies have become a major class of drugs globally.
Over the past decades, monoclonal antibody therapies have gained a substantial share of the pharmaceutical market. These therapies have become increasingly important in treating various diseases. Thus, based on technological advances, the development of these therapies has become quicker and more efficient, with an improved safety profile. Monoclonal antibodies may be produced via mouse hybridoma, phage display, transgenic mouse, and single B-cell methods.
Must Read: Future Trends and Challenges in the Field of Biochemical Assays
Importance of the ADA Assay in Monoclonal Therapy Development
Irrespective of the method of monoclonal antibody production, these biologics can be both highly effective and immunogenic. It implies that when administered to patients, they can elicit a strong immunological response in their body, reducing drug efficacy and causing adverse events. The ADA generated due to the immunologic response lowers the drug efficacy, while neutralizing antibodies may completely neutralize the drug. The ADAs and Nabs can alter the drug distribution and lead to increased clearance of the drug from the body, thereby reducing its half-life. The ADAs generated can modify the pharmacokinetic and pharmacodynamic properties of the monoclonal antibodies, leading to adverse outcomes such as fever, rash, difficulty in breathing, and anaphylaxis.
More than 90% of therapeutic proteins trigger immunogenic reactions. Initially, the origin of monoclonal antibodies (e.g., murine-based) was attributed to the cause of immunologic response. However, later attempts to produce humanized and chimeric monoclonal antibodies could not eliminate this issue entirely. Although the exact molecular pathway involved in the formation of ADA is still unknown, the effects of ADA can range from insignificant to severe and life-threatening consequences. Consequently, immunogenicity testing using the ADA assay and neutralizing antibody assay is a key step in developing monoclonal antibody therapy.
By detecting and quantifying the level of ADA, understanding the potential neutralization of the drug by NAbs, and the impact of ADAs on pharmacokinetic and pharmacodynamic properties of the therapy, ADA assays help to assess the immunogenicity and potential side effects of the monoclonal antibody therapy under development. ADA and NAb assays are routinely used for immunogenicity testing in preclinical and clinical trials. Early identification of potential immunogenicity issues can help avoid drug development challenges later. It can also save substantial time, effort, and money involved in drug development. Furthermore, it provides an opportunity to optimize the drug design and thereby reduce immunogenicity.Immunogenicity testing is an elaborate process. Since drug discovery and development is a complex and lengthy process, spanning several years, pharmaceutical giants rely on institutions, universities, and contract research organizations for bioanalytical testing support. It helps pharma companies through cost-saving, increased efficiency, and access to specialized expertise, allowing them to focus on their core competencies of drug development. These external organizations offer a diverse range of Bioanalysis Services, including immunogenicity testing services such as the development and validation of qualitative and quantitative assays, routine implementation, and end-to-end support with the assays developed.
