The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling

Figure 6

Aggregates could not enhance ADA production by increasing number of epitopes if high affinity epitopes are already present in nonaggregated TPP. Simulated levels of TPP in endosome, epitope in endosome, MHC II-peptide complex on cell surface, and ADA production are shown for ((a)–(d)) original two predicted epitopes for nonaggregated adalimumab [47, 48], ((e)–(h)) three epitopes for hypothetical aggregated form, and ((i)–(l)) four epitopes for hypothetical aggregated form. The predicted dissociation constant (, unit: nM) for binding of each epitope to MHC II is indicated. ADA production has the same definition and dose has the same value as in Figure 4.