Nano-Science Seminar: Thomas Andresen
In the present work we investigate re-modulation of the tumor microenvironment and activation of the adaptive immune system by combinations of nanocarrier based chemotherapy and Toll TLR7 agonists. We utilized spatial and temporally controlled delivery of oxaliplatinum using nanocarrier systems to induce effective immunogenic cancer cell death, eradication of myeloid derived suppressor cells (MDSCs) and macrophages in the tumor microenvironment. Successive modulation of antigen presenting cells that re-populate the tumor tissue using resiquimod (R848) towards a pro-inflammatory state resulted in a highly efficacious anticancer response that ultimately provided T cell memory. We obtained complete response and overall survival in 70% animals without remission after >100 days. The study was carried out in a CT26 syngeneic cancer model for >100 days where all surviving animals were immunized against re-challenge. We found that this effect was primarily generated by reduction of MDSCs in the tumor microenvironment and enhanced CD8 T cell specificity towards tumor antigens resulting in effective eradication of cancerous cells. The combination of using a nanocarrier system of oxaliplatiunum and R848 was unique for obtaining this response.