Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5857967 | Reproductive Toxicology | 2016 | 58 Pages |
Abstract
An enhanced embryo-fetal development study was conducted in cynomolgus monkeys using pateclizumab, a humanized IgG1 monoclonal antibody (mAb) targeting lymphotoxin-alpha. Pateclizumab administration between gestation days (GD) 20 and 132 did not induce maternal or developmental toxicities. The ratio of fetal-to-maternal serum concentration of pateclizumab was 0.73% on GD 50 and 61% by GD 139. Decreased fetal inguinal lymph node-to-body weight ratio was present in the high-dose group without microscopic abnormalities, a change attributable to inhibition of lymphocyte recruitment, which is a pharmacologic effect of pateclizumab during late lymph node development. The effect was observed in inguinal but not submandibular or mesenteric lymph nodes; this was attributed to differential susceptibility related to sequential lymph node development. Placental transfer of therapeutic IgG1 antibodies; thus, begins during the first trimester in non-human primates. Depending on the potency and dose levels administered, antibody levels in the fetus may be pharmacologically or toxicologically relevant.
Keywords
HEVslymphotoxin αTNFCmaxFDCsR-PhycoerythrinmAbFITCLTαAPCTNFRATANHPRheumatoid arthritisallophycocyaninMonoclonal antibodyTherapeutic monoclonal antibodyElectrochemiluminescence assayPlacental transferImmunohistochemistryIHCToxicokineticsIntravenousEmbryo-fetal developmentsubcutaneousFollicular dendritic cellsIntramuscularPharmacodynamicsPharmacokineticstumor necrosis factorfluorescein isothiocyanateLymphotoxin alphanon-human primatehigh endothelial venulesECLATNF receptor
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Authors
Hong Wang, Chris Schuetz, Akihiro Arima, Yutaka Chihaya, Gerhard F. Weinbauer, Gunnar Habermann, Jim Xiao, Cynthia Woods, Jane Grogan, Thomas Gelzleichter, Gary Cain,