.png){kind=icon}
.png){kind=icon}
Return
A comprehensive evaluation of the human Tg32 and Tg276 FcRn transgenic mouse and non-human primate models for predicting antibody pharmacokinetics in human
.png){kind=icon}
OA
AI
M
M
C
V
C
E
G
N
A
DOI：10.1080/19420862.2026.2668888.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
In this study, we present a comprehensive evaluation of two human FcRn transgenic mouse models, Tg276 and Tg32, demonstrating their ability to predict the pharmacokinetic (PK) parameters of IgG-type antibodies in human and monkey (non-human primate, NHP), including molecules with and without half-life extension. To assess the translational relevance of the humanized FcRn mouse models, we integrated a broad dataset comprising in vivo PK parameters in both animals and humans derived from the literature and in-house experiments. Using this dataset, we optimized scaling exponents, performed allometric scaling, and evaluated the predictive performance of the models. The optimized exponents fell within expected ranges, 0.7 to 0.95 for systemic and intercompartmental clearance, and around 1 for central and peripheral volumes of distribution. Our analysis reveals the need to apply distinct scaling exponents for half-life extended versus non-extended antibodies, as well as model-specific exponents. The results demonstrate that human PK predictions from Tg32 and Tg276 mice are comparable to those from the NHP. These models therefore offer a good alternative to the monkey, potentially reducing the need to conduct early in vivo PK studies in NHPs. We also report for the first time the use of an immunocompromised version of the Tg276 model to mitigate anti-drug antibody responses. Our findings show that the Tg276 hemizygous model exhibits a translational performance equal to, and in some cases superior to, that of the Tg32 homozygous strain and the NHP, specifically, in terms of predicted clearance. These insights support the Tg276 model as a valuable tool for early-stage antibody screening and lead optimization in preclinical PK evaluation.
Keywords:
Allometric scaling
Fc-engineered antibodies
FcRn
non-human primate
monkey
pharmacokinetics
Tg276
Tg32
Journal
IF:
7.3
Papers:
1.8K
Citations:
7.2K
Organization
Cited Papers