Almost all therapeutic proteins (biological agents) elicit an immune response with the subsequent production of anti-drug antibodies (ADAs). The majority of ADA against therapeutic monoclonal antibodies (mAbs) are directed against the antigen-binding sites of therapeutic mAbs and are therefore neutral. This type of ADA response explains why fully human antibodies can still be highly immunogenic.
The high heterogeneity between ADA assays prevents direct comparisons of immunogenicity between different molecules and between studies. IC ADA formation of a drug can significantly alter the pharmacokinetics and directly reduce drug efficacy if the ADA titer is high and sufficiently stable. You can also contact us to know more about ADA antibodies.
In patients with low ADA titers, the free drug concentration may remain high enough to be effective, whereas in patients who develop high ADA titers, most of the drug is neutralized and clinical failure is possible. ADA can also increase the risk of side effects, namely hypersensitivity reactions.
Several studies have demonstrated the presence of ADA before clinically apparent side effects, underlining its prognostic value. Algorithms that integrate therapeutic pharmacovigilance and immunogenicity information into the ongoing clinical evaluation of patients receiving biologics are now available to guide therapeutic decisions in clinical practice and help us develop safer and more cost-effective therapeutic strategies.
The increasing use of multiple immunomodulatory agents (IMD) for cancer therapy raises questions about their potential immunogenicity and treatment effects. In this review, we outline the mechanism of action (MOA) of approved antibody-based IMD drugs that may be related to their immunogenicity and discuss the reported incidence of antidote antibodies (ADA) and their clinical relevance in cancer patients.