Functional humanization of immunoglobulin heavy constant gamma 1 Fc domain human

Document Type

Article

Publication Date

2020

Keywords

JMG

JAX Source

Mabs 2020; 12(1):1829334

Volume

12

Issue

1

First Page

1829334

Last Page

1829334

ISSN

1942-0870

PMID

33025844

DOI

https://doi.org/10.1080/19420862.2020.1829334

Grant

OD011190

Abstract

A major asset of many monoclonal antibody (mAb)-based biologics is their persistence in circulation. The MHC class I family Fc receptor, FCGRT, is primarily responsible for this extended pharmacokinetic behavior. Engagement of FCGRT with the crystallizable fragment (Fc) domain protects IgG from catabolic elimination, thereby extending the persistence and bioavailability of IgG and related Fc-based biologics. There is a need for reliable in vivo models to facilitate the preclinical development of novel IgG-based biologics. FcRn-humanized mice have been widely accepted as translationally relevant surrogates for IgG-based biologics evaluations. Although such FCGRT-humanized mice, especially the mouse strain, B6.Cg-Fcgrt

Comments

The authors would like to thank Cindy Avery and John Wilson for their excellent technical assistance in this work. Also, Pete Kutny and the microinjection core for their expertise and dedication as well as Simon Lesbirel and the Genome Technology core at The Jackson Laboratory. We also gratefully acknowledge the contribution of Melissa Berry, Derry Roopenian for suggested experimental design and writing and also the Genome Technologies Service and Genetic Engineering Technologies at The Jackson Laboratory for expert assistance with the work described in this publication.

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