Immunogenicity assay development is crucial for biologics and other large-molecule drug products. Biotherapeutics have the potential to induce unwanted immune responses. However, immunogenicity testing differs from general efficacy studies involved with vaccine development. Immunogenicity testing detects and evaluates anti-drug bodies produced against a biological or large molecule drug.
Immunogenicity testing services focus on detecting unwanted immune responses. A biotherapeutic inducing wanted immune responses may lead to adverse reactions and affect the efficacy of a drug product. Hence bioanalytical methods for detecting anti-drug antibodies are vital for developing new biopharmaceuticals. Today several ligand binding and immunoassays are available for ADA detection. The current article dives deep into the reality behind anti-drug antibody immune responses and immunogenicity testing.
Working of the Immune System
The immune system is a defense mechanism to protect against foreign invaders, for example, viruses. Once a virus enters the body, the immune system detects it and employs destroying systems to kill the virus. In a nutshell, the immune system identifies a foreign invader, determines whether or not they are wanted or unwanted, inactivates them, and eventually destroys and inserts a memory to respond against a similar entity more quickly the next time.
Among different systems in the immune responses, B cells and T cells are the primary cellular network responsible for identifying and killing intruders. B cells produce antibodies that bind to the virus and stop its infection process. On the other hand, T cells are secondary units that recognize infected cells and destroy them.
Vaccines are designed to prompt a natural immune response. Vaccines are generally inactive components of a virus that invokes a less intensive immune response in the body. They generate both T-cell and B-cell immune responses. Usually, vector vaccines employ a modified system of the virus to deliver the components and prime the immune system.
Today biopharmaceuticals based on proteins, antibodies, and related biological materials have become common. Besides, the specificity of monoclonal antibodies has made them a popular choice of therapy against complex diseases such as cancer and autoimmune disease. However, monoclonal antibodies are foreign to the body and may induce an unwanted immune response when administered to an individual. These unwanted outcomes can range from simple reactions to life-threatening events. However, in the absence of any adverse events, unwanted immunogenicity may affect the efficacy of a drug product.
Today ADA levels are considered measures of unwanted immune responses against biotherapeutic agents. Besides, anti-drug antibodies can affect bioavailability, pharmacokinetics, and pharmacodynamics properties, eventually affecting efficacy. Generally, anti-drug antibodies can be divided into neutralizing and non-neutralizing ADAs. Neutralizing anti-drug antibodies can block and interfere with the activity of a drug product and its ability to bind its target. On the other hand, non-neutralizing antibodies bind to specific target regions of a drug product that do not affect its binding abilities. Therefore, identifying and assessing neutralizing anti-drug antibodies are crucial in drug development, as it directly affects a drug’s ability to impart its desired therapeutic effects.
To conclude, immunogenicity testing forms an integral component of biotherapeutic drug development. However, having an in-depth understanding of immune responses is crucial for designing and developing a robust immunogenicity testing protocol.