Effects of ICOS+ T cell depletion via afucosylated monoclonal antibody MEDI-570 on pregnant cynomolgus monkeys and the developing offspring.

Authors:
Gianluca Carlesso
Lily I Cheng
Lily I Cheng
National Institute of Allergy and Infectious Diseases
United States
Halie Cook
Halie Cook
Toxicology
Reston | United States
Karma Dacosta
Karma Dacosta
Department of Pathology
Joel Leininger
Joel Leininger
University of Pittsburgh Cancer Institute
United States

Reprod Toxicol 2017 12 13;74:116-133. Epub 2017 Sep 13.

Toxicology, Research & Development, MedImmune Inc., One MedImmune Way, Gaithersburg, MD 20854, United States.

MEDI-570 is a fully human afucosylated monoclonal antibody (MAb) against Inducible T-cell costimulator (ICOS), highly expressed on CD4+ T follicular helper (T) 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.

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http://dx.doi.org/10.1016/j.reprotox.2017.08.018DOI Listing
December 2017
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