Enhanced tumor-targeting selectivity by modulating bispecific antibody binding affinity and format valence.

ABSTRACT: Bispecific antibodies are considered attractive bio-therapeutic agents owing to their ability to target two distinct disease mediators. Cross-arm avidity targeting of antigen double-positive cancer cells over single-positive normal tissue is believed to enhance the therapeutic efficacy, restrict major escape mechanisms and increase tumor-targeting selectivity, leading to reduced systemic toxicity and improved therapeutic index. However, the interplay of factors regulating target selectivity is not well understood and often overlooked when developing clinically relevant bispecific therapeutics. We show in vivo that dual targeting alone is not sufficient to endow selective tumor-targeting, and report the pivotal roles played by the affinity of the individual arms, overall avidity and format

SUBMITTER: Mazor Y 

PROVIDER: S-EPMC5220356 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature