Improving Tumor Penetration of Antibodies and Antibody-Drug Conjugates: Taking Away the Barriers for Trojan Horses

The high affinity of an antibody can result in restricted tumor penetration and heterogenous tumor distribution, with preferential binding of the antibody to tumor cells localized around tumor vasculature. This so-called binding site barrier effect limits the efficacy of antibody-based therapies like antibody-drug conjugates (ADC). In this issue, Bordeau and colleagues introduce an original approach to overcome this barrier through transient competitive inhibition of antibody-antigen binding. By coadministration of an anti-idiotypic anti-trastuzumab domain antibody as a competitive inhibitor, increased tumor penetration of trastuzumab as well as enhanced efficacy of the ADC ado-trastuzumab emtansine were observed in tumor-bearing mice

Automated summary

The high affinity of an antibody can lead to restricted tumor penetration and heterogeneous distribution, limiting the efficacy of antibody-based therapies. By competitively inhibiting antibody-antigen binding, increased tumor penetration of the antibody and enhanced efficacy of ADCs can be achieved.