Influence ofFCGRTgene polymorphisms on pharmacokinetics of therapeutic antibodies

• DOI: 10.4161/mabs.24815
• Publication Date: 2013-04-25T20:59:26Z
• Authors: Christophe Passot; Nicolas Azzopardi; Sylvaine Renault; Nadine Baroukh; Christophe Arnoult; Marc Ohresser; Michèle Boisdron-...; Erick Gamelin; Hervé Watier; Gilles Paintaud; Valérie Gouilleux...
• Keywords: TaqMan; Neonatal Fc receptor

The neonatal Fc receptor (FcRn) encoded by FCGRT is known to be involved in the pharmacokinetics (PK) of therapeutic monoclonal antibodies (mAbs). Variability expression gene and consequently FcRn protein level could explain differences PK observed between patients treated with mAbs. We studied whether previously described variable number tandem repeat (VNTR) or copy variation (CNV) are associated individual variations parameters cetuximab. VNTR CNV were assessed on genomic DNA 198 healthy individuals 94 mAb. analyzed allele-specific PCR duplex real-time Taqman® technology, respectively. relationship polymorphisms (VNTR CNV) cetuximab was studied. VNTR3 homozygote had a lower distribution clearance than VNTR2/VNTR3 VNTR3/VNTR4 (p = 0.021). no affects genotype elimination clearance. One person (0.5%) 1 patient (1.1%) 3 copies FCGRT. this did not differ from those 2 copies. promoter may influence mAbs' body. cannot used as relevant pharmacogenetic marker because its low frequency.