Immunogenicity screening in protein drug development.
Most therapeutic proteins in clinical trials or on the market are, to a variable extent, immunogenic. Formation of antidrug antibodies poses a risk that should be assessed during drug development, as it possibly compromises drug safety and alters pharmacokinetics. The generation of these antibodies is critically dependent on the presence of T helper cell epitopes, which have classically been identified by in vitro methods using blood cells from human donors. As a novel development, in silico methods that identify T cell epitopes have been coming on line. These methods are relatively inexpensive and allow the mapping of epitopes from virtually all human leukocyte antigen molecules derived from a wide genetic background. In vitro assays remain important, but guided by in silico data they can focus on selected peptides and human leukocyte antigen haplotypes, thereby significantly reducing time and cost.
Van Walle
Ivo
I
Algonomics NV, Technologiepark 4, 9052 Gent-Zwijnaarde, Belgium. ivo.van.walle@algonomics.com
Gansemans
Yannick
Y
Parren
Paul W H I
PW
Stas
Philippe
P
Lasters
Ignace
I
D000818:Animals; D000917:Antibody Formation; D002986:Clinical Trials as Topic; D015195:Drug Design; D000939:Epitopes; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D011506:Proteins / Q000276:immunology / Q000627:therapeutic use*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000939:Epitopes; D006680:HLA Antigens; D011506:Proteins