Preclinical pharmacokinetics of a recombinant humanized rabbit anti-VEGF monoclonal antibody in rabbits and monkeys.

Autor: Yu DA; Jiangsu T-mab BioPharma Co., Ltd, Taizhou, Jiangsu, China., You M; Jiangsu T-mab BioPharma Co., Ltd, Taizhou, Jiangsu, China., Ji WW; Jiangsu T-mab BioPharma Co., Ltd, Taizhou, Jiangsu, China., Lu Y; Jiangsu T-mab BioPharma Co., Ltd, Taizhou, Jiangsu, China., Liu B; WestChina-Frontier PharmaTech Co., Ltd, Chengdu, China., Yan SS; Jiangsu T-mab BioPharma Co., Ltd, Taizhou, Jiangsu, China. Electronic address: shoushengyan@t-mab.com.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2018 Aug; Vol. 292, pp. 73-77. Date of Electronic Publication: 2018 Apr 27.
DOI: 10.1016/j.toxlet.2018.04.031
Abstrakt: TMAB001 is a humanized rabbit monoclonal antibody (mAb) designed to bind and neutralize human vascular endothelial growth factor (VEGF)-165. The purpose of the study was to investigate the pharmacokinetics (PK) and ocular tissue distribution after a single intravitreal (IVT) dose in rabbits and monkeys. Rabbits (2.5 mg/eye; n = 40) and monkeys (2.5 mg/eye; n = 12) received TMAB001 as a bilateral IVT dose. TMAB001 concentrations were measured in ocular tissues in all rabbits and monkeys by enzyme-linked immunosorbent assay (ELISA). TMAB001 and VEGF concentrations were measured in serum of monkeys by ELISA. Following a single bilateral IVT injection of TMAB001 2.5 mg/eye, the highest concentration was in vitreous humor, followed by retina and choroid, and the lowest concentration was in lens. In rabbits, TMAB001 was still detectable in ocular tissues at day 21 after single IVT dose, with the highest level in the vitreous humor and then retina, with longest t 1/2 in aqueous humor and shortest t 1/2 in choroid. In monkeys, t max in serum was 43 h and t 1/2 was approximately 5.5 days. C max in serum was much lower than that in vitreous, nearly 1/200. After IVT injection of TMAB001, total VEGF concentrations in serum and ocular tissues increased over time. VEGF concentration in retina and choroid increased over time, up to 336 h after administration. This study demonstrated that TMAB001 could reach the drug target sites-retina and choroid after a single bilateral IVT administration in rabbits and monkeys, with a long t 1/2 in vitreous humor. TMAB001 also showed strong capability to neutralize VEGF. The study further confirmed that full-length antibodies can also efficiently diffuse and distribute in ocular tissues.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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