CpG Liposomes Activate Antigen Presenting Cells for Cancer Immunotherapy
Ashley Widmer, Haojun Zhang, Alex Francian, Max Kullberg
University of Alaska, Anchorage
Tumor-mediated immune evasion is a defining characteristic of cancer. CpG oligodeoxynucleotides (CpG ODNs) have been shown to activate antigen presenting cells (APCs) by binding to Toll-like receptor 9 (TLR-9), which is expressed in the endoscopes of leukocytes. However, when injected, CpG is quickly broken down by DNases and can result in systemic release of cytokines and severe toxicity. To improve on delivery to APCs, our lab has recently developed a liposome that binds complement C3 (C3-liposomes), resulting in efficient uptake by APCs. Here, we show that CpG encapsulated in C3-liposomes results in potent activation of human APCs.
In this study, CpG ODNs were encapsulated in C3-liposomes and used to treat monocytes isolated from healthy patient whole blood. APCs, including dendritic cells and macrophages, were shown to internalize C3-liposomes and subsequently significantly increase co-stimulatory molecules, including CD80, CD83, CD86, and CD40, on their cell surface when compared to controls. Analysis by RT-PCR showed up-regulation of IL-1β, a key mediator of the inflammatory response, in CpG encapsulated C3 liposome treated monocytes. These results show that CpG encapsulated C3-liposomes stimulate APCs, which could enhance cancer immunotherapy.
Funded by BUILD EXITO, a National Institutes of Health (NIH)-funded initiative, an Institutional Development Award (IDeA) from the NIH, and by The Alaska Run for Women