Strategies to enhance monoclonal antibody uptake and distribution in solid tumors

Despite the significant resources dedicated to the development of monoclonal antibody(m Ab) therapies for solid tumors, the clinical success, thus far, has been modest. Limited efficacy of m Ab in solid tumors likely relates to unique aspects of tumor physiology. Solid tumors have an aberrant vasculature and a dense extracellular matrix that slow both the convective and diffusive transport of m Abs into and within tumors. For m Abs that are directed against cellular antigens, high antigen expression and rapid antigen turnover can result in perivascular cells binding to and eliminating a significant amount of extravasated m Ab, limiting m Ab distribution to portions of the tumor that are distant from functional vessels. Many preclinical investigations have reported strategies to improve m Ab uptake and distribution; however, to our knowledge, none have translated into the clinic. Here, we provide an overview of several barriers in solid tumors that limit m Ab uptake and distribution and discuss approaches that have been utilized to overcome these barriers in preclinical studies.