Factors impacting the tumor localization and distribution of antibody-based therapeutics in oncology

Abstract

Distribution of antibody-based therapeutics from the vascular space to the target tumor compartment is an important consideration in designing antibody-based oncology drugs. Mouse tumor models represent a reasonable approach for exploring antibody biodistribution. In general, a number of factors such as molecular size, antibody dose, and the length of in vivo tumor exposure can influence antibody localization and tumor penetration. With a few exceptions, the current available data indicate that at clinically relevant doses (ranging from 1 to 10 mg/kg) and over a reasonable clinical exposure time (days rather than hours), antibody biodistribution into tumors is unlikely to be the most significant factor hindering the clinical efficacy of antibody-based therapeutics. Other factors such as antigenic heterogeneity leading to variable distribution of antibody drugs into the tumor, or intrinsic resistance to antibody-mediated effects, may play a far greater role in the resistance properties impacting the antibody efficacy profiles.