A neutralizing antibody is responsible for defending against pathogens that may cause disease. Our body produces neutralizing antibodies through its immune responses. Generally, neutralizing antibodies help attain lifelong immunity against infections. Although they are crucial components of the immune system, neutralizing antibodies (NAb) produced against biotherapeutic or large molecule drug products render the drug product ineffective.
Immunogenicity testing is concerned with anti-drug antibody (ADA) analysis. Anti-drug antibodies can affect the bioavailability, pharmacokinetics, and pharmacodynamic properties of a drug product. Neutralizing antibody assays are a crucial component of ADA studies. After screening and confirming anti-drug antibodies, researchers begin with NAb assay development to test the neutralizing capacity of anti-drug antibodies. Hence neutralizing antibody assays are vital for ADA clinical trials. The current article explores neutralizing antibody assays in immunogenicity testing.
Neutralizing antibody assays
If investigators observe immunogenicity during clinical trials, NAb assays are required to assess the immunogenicity and neutralizing capacities of a product. If neutralizing antibodies affect drug efficacy, a large number of doses will be required to elicit a small therapeutic effect. Hence it is crucial to identify ADA and also to assess its neutralizing capacities.
Generally, neutralizing antibody assays are in vitro cell-based assays. Researchers design distinct cell-based assays to detect neutralizing antibodies. The mechanism of drug action will also be observed in a cell-based assay, which is specific to the target and mechanism of action of a drug product. Generally, these are cell-based assays, including potency bioassays. However, utmost care should be taken to consider matrix effects as they may require additional optimization of all assay components.
The Meso Scale Discovery platform is a robust instrument for analyzing neutralizing antibodies. MSD-based NAb assays have increased dynamic range, decreased matrix effects, and enhanced sensitivity. Besides, it requires fewer samples and study reagents. Moreover, besides binding assays, ELISA and enzymatic assay options are available for assessing neutralizing antibodies.
Significance of neutralizing antibody assays
Most large-molecule drug products, such as gene therapy or biologics, can potentially induce an immune response in the patient population. These antibodies can bind to the active sites of a drug product, decreasing its efficacy. However, it’s also possible that anti-drug antibodies can be non-neutralizing antibodies. However, it is mandatory to confirm the neutralizing capacities of anti-drug antibodies.
As neutralizing antibodies can affect the safety and efficacy profile of a drug product, all regulatory requirements need the determination of neutralizing antibodies during clinical trials showing the presence of ADAs. Researchers design ligand binding or cell-based assays to confirm neutralizing antibodies and gather data about the type and strength of immune response elicited by a drug product. These requirements make neutralizing antibody assays crucial for developing most large-molecule drug products.
Although neutralizing antibody assays can be complex and challenging, drug developers have the alternatives of immunogenicity testing services to help them assess the neutralizing capacities of anti-drug antibodies. With the growing demands on drug developers, the trend of outsourcing immunogenicity testing to reliable bioanalytical partners will only skyrocket in the coming future. However, staying up-to-date with regulatory requirements will be the key to a robust immunogenicity testing initiative.
