Trastuzumab does not bind rat or mouse ErbB2/neu: implications for selection of non-clinical safety models for trastuzumab-based therapeutics.

ABSTRACT:

Purpose

Assessment of non-clinical safety signals relies on understanding species selectivity of antibodies. This is particularly important with antibody-drug conjugates, where it is key to determine target-dependent versus target-independent toxicity. Although it appears to be widely accepted that trastuzumab does not bind mouse or rat HER2/ErbB2/neu, numerous investigators continue to use mouse models to investigate safety signals of trastuzumab and trastuzumab emtansine (T-DM1). We, therefore, conducted a broad array of both binding and biologic studies to demonstrate selectivity of trastuzumab for human HER2 versus mouse/rat neu.

Methods

Binding of anti-neu and anti-HER2 antibodies was assessed by ELISA, FACS, IHC, Scatchard, and immunoblot methods in human, rat, and mou

SUBMITTER: Lewis Phillips G 

PROVIDER: S-EPMC8763818 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature