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Effects of ICOS+ T cell depletion via afucosylated monoclonal antibody MEDI-570 on pregnant cynomolgus monkeys and the developing offspring.
- Source :
-
Reproductive toxicology (Elmsford, N.Y.) [Reprod Toxicol] 2017 Dec; Vol. 74, pp. 116-133. Date of Electronic Publication: 2017 Sep 13. - Publication Year :
- 2017
-
Abstract
- MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (T <subscript>FH</subscript> ) cells. Effects of MEDI-570 were evaluated in an enhanced pre-postnatal development toxicity (ePPND) study in cynomolgus monkeys. Administration to pregnant monkeys did not cause any abortifacient effects. Changes in hematology and peripheral blood T lymphocyte subsets in maternal animals and infants and the attenuated infant IgG immune response to keyhole limpet hemocyanin (KLH) were attributed to MEDI-570 pharmacology. Adverse findings included aggressive fibromatosis in one dam and two infant losses in the high dose group with anatomic pathology findings suggestive of atypical lymphoid hyperplasia. The margin of safety relative to the no observed adverse effect level (NOAEL) for the highest planned clinical dose in the Phase 1a study was 7. This study suggests that women of child bearing potential employ effective methods of contraception while being treated with MEDI-570.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Animals, Newborn
Antibodies, Monoclonal immunology
Antibodies, Monoclonal, Humanized
Embryo, Mammalian immunology
Embryonic Development immunology
Female
Fetal Development immunology
Fetus drug effects
Hemocyanins pharmacology
Immunoglobulin G immunology
Inducible T-Cell Co-Stimulator Protein immunology
Lymphocyte Count
Macaca fascicularis
Male
Maternal-Fetal Exchange
Pregnancy
Antibodies, Monoclonal administration & dosage
Inducible T-Cell Co-Stimulator Protein metabolism
Lymphocyte Depletion
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-1708
- Volume :
- 74
- Database :
- MEDLINE
- Journal :
- Reproductive toxicology (Elmsford, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 28916434
- Full Text :
- https://doi.org/10.1016/j.reprotox.2017.08.018