HER2 mutation-specific T cell engager for cancer

A bispecific T cell engager antibody selective for the two most common mutations in the HER2 extracellular domain could help selectively eliminate HER2-mutant cancer cells.

Screening of a human synthetic antibody phage library for binding to HER2 S310F and S310Y mutants, followed by affinity maturation, heavy chain engineering to eliminate a potential N-glycosylation site, deep mutational scanning and structure-guided optimization, yielded three antibodies with KD values in the low nanomolar range for the HER2 mutants, but no binding to wildtype HER2 at 100 nM. ...