[cv]

Improving therapeutic antibody delivery to solid tumors

As agents for cancer therapy, antibodies hold great promise due to their inherent selectivity for cancer antigens and lack of off-target effects compared to conventional systemic chemotherapy or radiation.  However, penetration of antibodies and other therapeutic macromolecules into solid tumors is poor, leading to large regions of untreated cancer cells within the tumors.  We hypothesize that this heterogeneous distribution of antibodies is an important factor limiting the efficacy of these drugs.  We propose to address this problem by first constructing a mathematical model of antibody extravasation within a vascularized solid tumor.  This model will be used to identify the key rate limiting parameters preventing efficient antibody distribution within the tumor, as well as to design strategies to modify these parameters.  We will then pharmacologically alter these limiting parameters in an in vivo cancer model and attempt to optimize the dosing strategies and timing to enhance antibody delivery to solid tumors.