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TGF-β1 Monoclonal Antibody: Assessment of Embryo-Fetal Toxicity in Rats and Rabbits

TGF-β1 Monoclonal Antibody: Assessment of Embryo-Fetal Toxicity in Rats and Rabbits

Kim G Hilbish, Jennifer A Martin, Anja J Stauber, Tammye L Edwards, William J Breslin

Birth Defects Res B Dev Reprod Toxicol. 2016 Aug;107(4-5):174-184.

PMID: 27519584

Abstract:

A humanized monoclonal antibody targeting transforming growth factor β1 (TGF-β1 mab) has been used in development for the treatment of chronic kidney disease. Embryo-fetal development studies were conducted in rats and rabbits using 30 and 25 animals per group, respectively. The TGF-β1 mab was administered subcutaneously to rats at 0, 2, or 50 mg/kg/dose on gestation days (GDs) 6, 10, and 14 and intravenously to rabbits at 0 or 3 mg/kg/dose on GDs 7, 12 to 19, and at 30 mg/kg/dose on GDs 7, 12, 14, 16, and 18. Maternal reproductive endpoints and fetal viability, weight, and morphology were evaluated. There was no indication of maternal or embryo-fetal toxicity in the rat. Effects in the rabbit were limited to the fetus where the 30 mg/kg TGF-β1 mab dose produced a slight decrease in fetal weight and an increase in the incidence of retrocaval ureter and an absent and/or malpositioned kidney/ureter in two fetuses. In conclusion, TGF-β1 mab produced no adverse maternal or embryo-fetal findings in rats when administered ≤50 mg/kg on GDs 6, 10, and 14. TGF-β1 mab did not demonstrate maternal toxicity or embryo-fetal lethality at doses as high as 30 mg/kg when administered on GDs 7, 12, 14, 16, and 18 in rabbits. Fetal growth and morphology were affected only at 30 mg/kg; thus, the no observed adverse effect level was 3 mg/kg in rabbits. The margin of safety for both rats and rabbits was ≥37-fold the clinical exposure level.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42417048	Anti-phospho-Integrin β1 (pThr789) antibody produced in rabbit			Price

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