Effect of the maternofetal and milk transfer of the anti-epidermal growth factor receptor monoclonal antibody 7A7 in mice

• Published in: Placenta (Eastbourne) 2011-06, Vol.32 (6), p.470-474
• Main Authors: González, J.E, León, M, Hernández, I, Garrido, G, Casacó, Á
• Format: Article
• Language: English
• Subjects: Animals; Anti-epidermal growth factor monoclonal antibodies; Antibodies, Monoclonal - immunology; Biological and medical sciences; Cancer treatment; Embryology: invertebrates and vertebrates. Teratology; Female; Fundamental and applied biological sciences. Psychology; Internal Medicine; Lactation - immunology; Male; Mice; Milk transfer; Obstetrics and Gynecology; Placental transfer; Pregnancy; Receptor, Epidermal Growth Factor - immunology
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2011.03.011

Abstract Objectives To study the maternofetal and milk transfer of an anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MAb) and its effects on conceptus, we administered to pregnant and lactating dams the murine anti-EGFR MAb 7A7 in an autologus model. Study design For determining the embryo-fetal toxicity, 7A7 at gestational days (GD) 6, 8, 12 and 14 were intravenously administered. Clinical signs and body weights were recorded. On GD 18 pregnant mice were euthanized and the alive and dead fetuses were examined. For measuring the maternofetal transfer mice were dosed on GD 14 with125 I-7A7, after 24 h, mice were euthanized and main maternal organs and fetuses were counted separately for radioactivity. For studying the MAb transferred throughout the milk, lactating dams were intravenously dosed on lactation day (LD) 2 with125 I-7A7. Blood samples were obtained from dams at different times post. One lactating pup from each dam was also euthanized at different times, and their blood and gastric milk were removed and the radioactivities measured. Results The administration of the 7A7 did not elicit toxicity to adult pregnant mice nevertheless; there was evidence of embryo-fetal toxicity in the 7A7 group characterized by a decrease in litters’ body weights and head deformities. The maternofetal transfer of125 I-7A7 antibody on GD 15 was only of a 4%. Conclusion Results suggest that 7A7 crosses placenta and it is transferred in a superior quantity to pups through the milk and that anti-EGFR MAbs have a potential toxic effect to fetuses.