Models for evaluation of relative immunogenic potential of protein particles in biopharmaceutical protein formulations.
An immune response to a therapeutic protein that compromises the biopharmaceutical activity or cross-reacts with an endogenous protein is a serious clinical event. The role of protein aggregates and particles in biopharmaceutical formulations in mediating this immune response has gained considerable attention over the recent past. Model systems that could consistently and reliably predict the relative immunogenicity of biopharmaceutical protein formulations would be extremely valuable. Several approaches have been developed in an attempt to provide this insight, including in silico algorithms, in vitro tests utilizing human leukocytes and in vivo animal models. This commentary provides an update of these various approaches as well as the author's perspectives on the pros and cons of these different methods.
Medical Products Division, Baxter Healthcare Corporation, Round Lake, Illinois, USA. richard_johnson@baxter.com
Richard
R
Johnson
Wim
W
Jiskoot
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001688:Biological Products / Q000009:adverse effects* / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D011506:Proteins / Q000009:adverse effects* / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use
D001688:Biological Products; D011506:Proteins; D014614:Vaccines, Synthetic