title: Assessment of placental transfer and the effect on embryo-fetal development of a humanized monoclonal antibody targeting lymphotoxin-alpha in non-human primates.
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.
authors.affiliation: Genentech Research and Early Development, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: wang.hong@gene.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Genentech Research and Early Development, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Schuetz
authors.affiliation: Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories, 2438 Miyanoura, Kagoshima 891-1394, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Arima
authors.affiliation: Shin Nippon Biomedical Laboratories, Ltd., Drug Safety Research Laboratories, 2438 Miyanoura, Kagoshima 891-1394, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Chihaya
authors.affiliation: Covance Preclinical Services GmbH, Kesselfeld 29, 48163 Munster, Germany.
authors.forename: Gerhard F
authors.initials: GF
authors.lastname: Weinbauer
authors.affiliation: Covance Preclinical Services GmbH, Kesselfeld 29, 48163 Munster, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Habermann
authors.affiliation: Genentech Research and Early Development, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Genentech Research and Early Development, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Woods
authors.affiliation: Genentech Research and Early Development, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Grogan
authors.affiliation: Genentech Research and Early Development, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gelzleichter
authors.affiliation: Genentech Research and Early Development, 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Cain
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D020566:Dendritic Cells, Follicular / Q000187:drug effects; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology; D008198:Lymph Nodes / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D008218:Lymphocytosis / Q000139:chemically induced; D008233:Lymphotoxin-alpha / Q000276:immunology*; D008252:Macaca fascicularis; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D008233:Lymphotoxin-alpha; C576689:pateclizumab
keywords: Embryo-fetal development; Lymphotoxin alpha; Non-human primate; Placental transfer; Sequential lymph node development; Therapeutic monoclonal antibody