Enhancing tumor antigen presentation with complement targeted liposomes Alexandra Francian, Madigan Stanley, Shelby Namen, Kristine Mann, Holly Martinson, Max Kullberg University of Alaska Anchorage, WWAMI School of Medical Education
Cancer immunotherapies strengthen the immune system's ability to recognize and eliminate cancer cells. Antigen presenting cells (APC) of the innate immune system drive immune activation and response to cancer by internalizing and presenting tumor associated antigens (TAA) to cells of the adaptive immune system. Recently, our lab has developed a liposomal nanoparticle which specifically targets APCs through the complement C3 receptor (C3-liposomes). These liposomes encapsulate tumor antigen and are formulated to bind a patient's endogenous complement C3 upon injection, leading to liposome uptake and antigen delivery to APCs. In this study, ovalbumin (OVA), a widely used model antigen, was encapsulated in C3-liposomes and used for in vitro and in vivo experiments. APCs were shown to internalize C3-liposomes and subsequently process encapsulated OVA for presentation via the major histocompatibility complex (MHC) receptors on their surface. C3-liposome delivery of OVA to APCs resulted in a significant increase in activation of OVA reactive T cells ex vivo, demonstrating the potential of C3-liposomes as a tumor antigen delivery tool.
To determine effectiveness in vivo, mice bearing a lymphoma cell line that expresses OVA as a tumor antigen (A20-OVA) were treated with C3-liposomes. Mice injected intratumorally with C3-liposomes containing OVA showed significantly reduced tumor growth of established tumors and complete eradication of injected and distal tumors in all but one mouse. These results demonstrate a systemic anti-tumor immune reaction in response to localized liposome delivery. Flow cytometry analysis of peripheral blood showed that mice treated with C3-liposomes had significantly lower percentages of immunosuppressive myeloid derived suppressor cells (MDSC), compared to controls. Mice treated with C3-liposomes also had higher percentages of antibody producing B cells, and higher levels of anti-OVA IgG1 in their blood plasma.
These results indicate that C3-liposomes efficiently deliver tumor antigen to APCs, resulting in a potent anti-tumor immune response.
Funded by an Institutional Development Award (IDeA) from the National Institutes of Health and by The Alaska Run for Women
Credits: None available.
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