Immunogenicity Risk Assessment In Drug Candidate Selection

Early identification of unwanted immune responses is critical for a drug candidate's success. An immune reaction can derail development, wasting time and resources. Detecting immunogenic risks early enables prioritization of low-risk molecules or strategic modifications to optimize candidates. Addressing these risks proactively streamlines development, minimizes setbacks, and accelerates progress—helping ensure clinical success.

The immune system recognizes therapeutic proteins as foreign based on factors like amino acid sequence, structure, PTMs, and formulation. Significant differences from natural proteins trigger anti-drug antibodies (ADAs), which can neutralize the drug, reduce efficacy, and cause side effects, especially if they cross-react with the body’s proteins. Immunogenicity refers to a molecule's ability to provoke such responses, initiated when APCs present protein fragments on MHC class II molecules, activating CD4+ T cells and leading to ADA production.