Immunogenicity
Sometimes immune responses to protein therapeutics are desired, such as when developing a vaccine, (Figure 2).
However, treatment with therapeutic proteins not meant as a vaccine can elicit an unwanted immune responses, such as the development of anti-drug antibodies (ADAs), produced by the B lymphocytes of the immune system in response to foreign proteins. ADAs can decrease the efficacy of the biologic protein treatments, and can cause high levels of clearance, induce hypersensitivity reactions, or cause severe adverse events1.
Causes of immunogenicity include factors related to:
- Drug structure
- Patient genetics (e.g HLA type)
- Patient disease state
- Route of administration
- Impurities
- Formulation
- Dose
- Target
- Animal origin
Regulatory expectations are that developers of non-vaccine biological therapeutics use validated immunogenicity assays to show whether ADA formation is a risk and what type of ADA might be formed. In preclinical immunogenicity assessment, FDA guidance mentions that in vivo animal models are not necessarily predictive for immunogenicity in human due to species differences, therefore in vitro immunogenicity assays based on innate and adaptive immune cells are recommended and could be helpful in revealing cell-mediated responses2, 3.