Correlation of FCGRT genomic structure with serum immunoglobulin, albumin and farletuzumab pharmacokinetics in patients with first relapsed ovarian cancer
| Autor: | Charles Schweizer, Nicholas C. Nicolaides, Rhonda Meredith, Wenquan Wang, Katie Bendas, Elizabeth B. Somers, Luigi Grasso, Mark Landers, Earl Albone, Jason Wustner, Daniel J. O'Shannessy, Susan C. Weil |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Folate Receptor Alpha Minisatellite Repeats Receptors Fc Pharmacology Antibodies Monoclonal Humanized Polymorphism Single Nucleotide 03 medical and health sciences chemistry.chemical_compound Cmin Neonatal Fc receptor Albumins Genetics Humans Ovarian Neoplasms biology Histocompatibility Antigens Class I Albumin Farletuzumab Carboplatin Variable number tandem repeat 030104 developmental biology Clinical Trials Phase III as Topic chemistry Immunoglobulin G biology.protein Female Neoplasm Recurrence Local Antibody |
| Zdroj: | Genomics. 109:251-257 |
| ISSN: | 0888-7543 |
| DOI: | 10.1016/j.ygeno.2017.04.006 |
| Popis: | Farletuzumab (FAR) is a humanized monoclonal antibody (mAb) that binds to folate receptor alpha. A Ph3 trial in ovarian cancer patients treated with carboplatin/taxane plus FAR or placebo did not meet the primary statistical endpoint. Subgroup analysis demonstrated that subjects with high FAR exposure levels (Cmin>57.6μg/mL) showed statistically significant improvements in PFS and OS. The neonatal Fc receptor (fcgrt) plays a central role in albumin/IgG stasis and mAb pharmacokinetics (PK). Here we evaluated fcgrt sequence and association of its promoter variable number tandem repeats (VNTR) and coding single nucleotide variants (SNV) with albumin/IgG levels and FAR PK in the Ph3 patients. A statistical correlation existed between high FAR Cmin and AUC in patients with the highest quartile of albumin and lowest quartile of IgG1. Analysis of fcgrt identified 5 different VNTRs in the promoter region and 9 SNVs within the coding region, 4 which are novel. |
| Databáze: | OpenAIRE |
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