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

Figure 5

Aggregates could not enhance ADA production through faster antigen internalization or degradation if high affinity epitopes are already present in nonaggregated TPP. Simulated levels of nonaggregated and aggregated TPP in endosome, epitopes in endosome, MHC II-peptide complex on cell surface, and ADA production are shown for ((a)–(d)) original internalization (IR₀ = 14.4 day⁻¹) and degradation (DR₀ = 17.28 day⁻¹) rate for nonaggregated adalimumab [47, 48], ((e)–(h)) 16.6IR₀ and DR₀ for hypothetical aggregated form, and ((i)–(l)) IR₀ and 16.6DR₀ for hypothetical aggregated form. ADA production has the same definition and dose has the same value as in Figure 4.