(REF. NO. 222-HB)
Background
Angiogenesis, or the formation of new blood vessels from the existing vasculature, promotes the metastatic potential of tumors by establishing connections to the existing vasculature. Targeting tumor vasculature is under investigation as a potential therapeutic strategy for cancers that have undergone angiogenesis. Pathological angiogenesis associates with formation of endothelial cells that express cell surface proteins that are not present on quiescent endothelial cells and may serve as targets for cancer chemotherapy. One such protein, known as tumor endothelial marker 7-related (TEM7R), also known as plexin domain-containing protein 2 (PLXDC2), is known to be overexpressed in endothelial cells of tumor stroma. As some of the TEM proteins, including TEM7R, encode extracellular domains and trans-membrane motifs, this makes them attractive targets for immunotherapeutic strategies.
Summary of the Invention
Fox Chase researchers have developed an antibody that specifically binds to an epitope of the extracellular domain of TEM7R. The putative extracellular domain of murine TEM7R was cloned, transfected into HEK293 cells, and the resulting protein purified. Isolation of TEM7R reactive antibodies from a naïve human phage display library was then performed and a high- affinity clone for the purified ECD was identified. The identified high-affinity clone was then utilized to construct a single chain fragment and an IgG1 antibody in mammalian cell culture. The antibody was confirmed to bind to its respective target antigen in live cell binding assays, and selectively target tumors in vivo and localize to the tumor vasculature. Internalization of an antibody-toxin conjugate was also successful, with cell death observed after administration in F9 cells.
Advantages
- Novel highly-specific native & chimeric ADC targeting tumor biomarker
- Theranostic for tumor vasculature in cancers that have undergone angiogenesis
Patent Status
US Patent # US 8,883,978 and # US 9,534,050