A Designer Strategy to Develop Novel Bispecific Cancer Therapeutic Antibodies.

Abstract

Therapeutic antibodies selectively targeting EPHA2 with or without co-targeting another receptor tyrosine kinase have been limited to date. By integrating state-of-art proteogenomic, ex vivo models, and short hairpin RNA screening approaches, a new designing strategy has now discovered a bispecific therapeutic antibody co-targeting EPHA2 and EGFR - which effectively inhibits tumor cell growth in various preclinical cancer models. This new antibody provides new tools to impair the acquired resistance to EGFR-directed therapies or co-target EPHA2 and EGFR in human tumor. See related article by El Zawily et al., p. 2686.