Nano-Ghost for Targeted Therapy of Metastatic Cancer

Combination therapies comprised of immunotherapy and targeted therapy, may improve clinical outcomes when treating metastases. Targeted therapies can induce tumor cell death by selective inhibiting molecular pathways, crucial for tumor growth. In response, immunotherapy can sensitize tumor cells to immune attack and enhance the cytotoxic response achieved with targeted therapy leading to a long-lasting remission. Effective treatment using such combinations, which often differ in their physicochemical properties and bioavailability, requires them to reach their diverse targets simultaneously.

To address this challenge we propose to utilize our novel targeted drug delivery system, termed Nano-Ghosts (NGs). The ability to entrap different therapeutics in the NGs, along with their multitude of cellular targets makes them uniquely adequate carriers for combination therapies. The NGs are vesicles produced from the plasma membrane of human mesenchymal stem cells (hMSCs), known for their natural targeting of multiple cancers and for being hypo-immunogenic. NGs were shown to retain MSC natural surface moieties and encompass their unique targeting capabilities.

The NGs were found to selectively target different human cancer cell lines and have most effectively targeted lung cancer cells. The NGs’ selective targeting capabilities were demonstrated in a variety of metastatic cancer cells (both human and murine cancer cells). Recently, we demonstrated that the NGs have selectively accumulated in the lungs of metastases-bearing mice, while rapidly clearing from all other blood-filtering organs. Furthermore, NGs loaded with a pDNA encoding a cancer-toxic gene (pPEX-NGs), dramatically inhibited established metastases in a metastatic orthotopic NSCLC.