Complement C3 mediated targeting of liposomes to granulocytic myeloid derived suppressor cells
Max Kullberg1, Holly Martinson1, Kristine Mann1
1WWAMI Biomedical Program, University of Alaska Anchorage, Anchorage, AK, United States.
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 Editor:
It 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.
Insights
Researchers developed a novel liposomal drug delivery system targeting granulocytic myeloid-derived suppressor cells (G-MDSCs) in cancer patients. This system selectively delivers drugs to G-MDSCs, potentially restoring anti-tumor immunity.
Area of Science:
- Immunology
- Drug Delivery Systems
- Cancer Biology
Background:
- Granulocytic myeloid-derived suppressor cells (G-MDSCs) accumulate in cancer patients, suppressing anti-tumor T cell responses.
- Targeting G-MDSCs is a strategy to enhance cancer immunotherapy.
- Existing methods for G-MDSC modulation are limited.
Purpose of the Study:
- To develop and characterize a liposomal drug delivery system that selectively targets G-MDSCs.
- To evaluate the in vitro and in vivo efficacy of this targeted liposomal system.
Main Methods:
- Development of liposomes designed to form disulfide bonds with activated complement C3.
- In vitro uptake studies using G-MDSCs and serum from C3 knockout mice.
- In vivo biodistribution analysis of liposomes in tumor-bearing mice.
Main Results:
- Liposomes were shown to be taken up by G-MDSCs in a C3-dependent manner in vitro.
- Systemic administration of liposomes resulted in significant incorporation by G-MDSCs in blood, tumor, spleen, liver, and lungs.
- Demonstrated selective targeting of G-MDSCs in vivo.
Conclusions:
- The developed liposomal system provides a versatile platform for targeted drug delivery to G-MDSCs.
- This approach holds promise for restoring anti-tumor immunity in cancer patients.
- Potential adjunct therapy for enhancing cancer immunotherapy.
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