UCLA researchers in the Department of Nanomedicine have developed antigen presenting cells (APCs) targeting nanoparticles to deliver STING (stimulator of interferon genes) agonists to the liver for metastatic cancer treatment.
BACKGROUND:
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy and estimated to become the second leading cause of cancer-related deaths by 2030. It is often diagnosed at advanced stages with the liver as the main site of metastases. The liver contains unique antigen presenting cells (APCs) that are programmed for a robust immunosuppressive environment. Not only does this promote cancer metastases, but the liver is a frequent site of cancer recurrence after “curative” treatment. Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs), members of liver APCs, provide an opportunity to intervene in metastatic disease by reprogramming the immunosuppressive APC function of these cells. Specifically the scavenger receptors (SRs) on the cells surface present a viable and promising target for organ-selective delivery of checkpoint inhibitors or other immuno-oncology therapeutics.
INNOVATION:
Dr. Andre E. Nel and colleagues in the Department of Nanomedicine at UCLA have developed intravenous-injectable polymeric nanoparticles that deliver STING (stimulator of interferon genes) to APCs in the liver. The nanoparticles are decorated with SR ligands, and contain immune stimulatory cyclic dinucleotides (CDNs). Once CDNs are inside of APCs, they can induce type I interferon production and activate immune cells to suppress liver metastases, as validated in in vitro studies. The development of a STING delivering nanoparticle platform constitutes a promising pathway to treating metastatic liver disease. Additionally, the technology can be expanded to multiple cancer types such as colon, lung, gastric and breast cancer beyond the initial focus on pancreatic cancer metastases.
APPLICATIONS:
• Drug delivery
• Nanomedicines
• Cancer immunotherapy
ADVANTAGES:
• Biocompatible materials (FDA approved surfactants)
• Site-specific target delivery
• Adjustable platform
STATE OF DEVELOPMENT:
Cellular studies in a myeloid cell line (PMA-primed THP-1 cells) confirmed the ability of the nanoparticles to induce IFN-β release and simulate immune function. In vivo validation studies are underway.