Complement C3 mediated targeting of liposomes to granulocytic myeloid derived suppressor cells

Abstract

In cancer patients, granulocytic myeloid derived suppressor cells (G-MDSCs) expand in number, infiltrating tumor and lymphatic tissues where they suppress an anti-tumor immune response. We report here the development of a liposomal drug delivery system that selectively targets G-MDSCs. The liposomes form a disulfide bond with activated complement C3 after intravenous injection and are taken up by G-MDSCs, which express the receptor for activated C3. In vitro experiments utilizing serum from a C3 knockout mouse demonstrate that G-MDSCs take up these liposomes in a C3-dependent manner. After systemic administration to tumor bearing mice, liposomes were incorporated by 22% of G-MDSCs in the blood and were also present in a percentage of G-MDSCs in the tumor (11%), spleen (22%), liver (35%) and lungs (26%). This liposomal system offers a versatile means of targeted drug delivery to G-MDSCs and could be an important tool for restoring anti-tumor immunity in cancer patients. From the Clinical EditorIt has been shown that the presence of granulocytic myeloid derived suppressor cells (G-MDSCs) in cancer patients suppress the tumor immune response of T cells. Many drugs can be used to reverse this process. In this article, the authors describe the development of a liposomal drug delivery system for targeted drug delivery to G- MDSCs. This system may prove to be useful adjunct in immunotherapy in the fight against cancers.