Antibody Targeting of Caveolae in Breast Tumors

摘要

In this project, the authors propose to compare, at the molecular level, protein expression in caveolae in tumor vs. normal endothelium to identify caveolar proteins unique to the tumor endothelium that can be used as molecular targets for therapeutic probes. They will use a novel technique developed in their lab for isolating caveolae from normal and tumor tissues at very high purity for both the proteomic analysis as well as for direct injection into mice for monoclonal antibody production. Antibodies found to be tumor caveolae-specific by Western analysis and immunostaining of tissue specimens will be assessed for tumor targeting in vivo by injecting them IV into a rat breast tumor model system. Their goal is to find a breast tumor- specific, caveolae-targeted monoclonal antibody that will efficiently target the tumor and also transport drug conjugates into and even across the tumor endothelium for direct delivery to the underlying tumor cells. This approach may permit tumor ablation through localized destruction of the tumor vascular endothelium as well as increase the efficacy of chemotherapeutic agents in the treatment of solid breast tumors by improving accessibility with effective transport across the endothelial cell barrier.