Structure-based engineering of pH-dependent antibody binding for selective targeting of solid-tumor microenvironment.

ABSTRACT: Recent development of monoclonal antibodies as mainstream anticancer agents demands further optimization of their safety for use in humans. Potent targeting and/or effector activities on normal tissues is an obvious toxicity concern. Optimization of specific tumor targeting could be achieved by taking advantage of the extracellular acidity of solid tumors relative to normal tissues. Here, we applied a structure-based computational approach to engineer anti-human epidermal growth factor receptor 2 (Her2) antibodies with selective binding in the acidic tumor microenvironment. We used an affinity maturation platform in which dual-pH histidine-scanning mutagenesis was implemented for pH selectivity optimization. Testing of a small set of designs for binding to the recombinant Her2 ectodomain l

SUBMITTER: Sulea T 

PROVIDER: S-EPMC6927761 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature