Nanometer-Scale, Particle-Based Immunotherapy for Cancer Treatment (LDRD Final Report: 17-LW-051)
Treating patients with highly invasive cancer remains a significant challenge in healthcare. In this project, we leveraged novel techniques in formulating small molecule drugs and vaccine adjuvants using biomimetic nanoparticles (referred to as nanolipoprotein particles) to develop a combination chemotherapy-immunotherapy regime. This therapy was evaluated in vitro and in vivo using a model of triple-negative, highly metastatic breast cancer. We observed that formulated chemotherapeutic drug doxorubicin had reduced toxicity/efficacy compared to free drug in vitro. However, we observed that the improved drug had improved localization to the tumor site in vivo. In our combined therapy (NLP-Dox/CpG), this increased delivery led to a decreased tumor volume over the control group (with and without accompanying adjuvant) that was on par with free doxorubicin. More importantly, we observed 100% survival of the group that received formulated doxorubicin with adjuvant, compared to all other groups. The NLP-Dox/CpG group also had the most animals with fewer than 250 metastatic cells in the lung, suggesting that this was the most effective at limiting metastatic invasion. Additionally, all groups that received the CpG treatment had one animal that did not have any detectable metastatic cells in the lung. This data suggests that this chemotherapeutic-immunotherapeutic regimen has potential for better outcomes and longer survival in treatment of metastatic cancer.