Open AccessA Mechanistic, Multiscale Mathematical Model of Immunogenicity for Therapeutic Proteins: Part 1—Theoretical Model
Author(s) -
Chen X,
Hickling TP,
Vicini P
Publication year - 2014
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1038/psp.2014.30
Subject(s) - immunogenicity , computational biology , computer science , biology , immunology , immune system
A mechanistic, multiscale mathematical model of immunogenicity for therapeutic proteins was formulated by recapitulating key biological mechanisms, including antigen presentation, activation, proliferation, and differentiation of immune cells, secretion of antidrug antibodies (ADA), as well as in vivo disposition of ADA and therapeutic proteins. This system‐level model contains three scales: a subcellular level representing antigen presentation processes by dendritic cells; a cellular level accounting for cell kinetics during humoral immune response; and a whole‐body level accounting for therapeutic protein in vivo disposition. The model simulations for in vivo responses against antigenic protein challenge are consistent with many known immunological observations. By simulating immune responses under various initial parameter conditions, the model suggests hypotheses for future experimental investigation and contributes to the mechanistic understanding of immunogenicity. With future experimental validation, this model may potentially provide a platform to generate and test hypotheses about immunogenicity risk assessment and ultimately aid in immunogenicity prediction. CPT Pharmacometrics Syst. Pharmacol . (2014) 3, e133; doi: 10.1038/psp.2014.30 ; published online 03 September 2014