UC Irvine

Although progress has been made in conventional cancer therapy, cancer is still the second leading cause of death in the United States. Recently, a new approach for cancer treatment known as immunotherapy has shown remarkable success. Within immunotherapy, cancer vaccines train the body to recognize tumor-associated antigens for targeted destruction of cancer cells. While promising, clinical success of cancer vaccines to date has been limited. Our work focuses on utilizing a viral-mimetic design to develop a new platform to improve cancer vaccine efficacy. We have been exploring the non-viral E2 protein nanoparticle as a cancer vaccine platform. We verified that simultaneous delivery of cancer antigen epitopes (e.g., gp100, NY-ESO-1, MAGE-A3) and adjuvant (CpG) within E2 nanoparticles resulted in improved anti-tumor responses. Prophylactic immunization with CpG-gp-E2 (E2 conjugated with gp100 and CpG) increased animal survival time by ̴ 40% in an aggressive tumor model. Furthermore, we demonstrated that simultaneous delivery of human-restricted cancer-testis epitopes and CpG within E2 (CpG-NYESO-E2 and CpG-MAGE-E2) resulted in an increase in IFN-γ secretion and enhanced lytic activity towards human cancer cells expressing the antigen. These results demonstrate the broad efficacy of the E2 nanoparticle platform against various target cancer antigens.One of the promising new FDA-approved approaches in cancer immunotherapy is the obstruction of inhibitory effects of immune checkpoint molecules (e.g., PD-1). However, treatments with checkpoint inhibitors are still not effective in a significant portion of patients. To address this, we examined the therapeutic effects of combination delivery of anti-PD-1 with CpG-gp-E2 nanoparticles. In the B16-F10 melanoma tumor model, ̴ 50% of the mice treated with combination therapy remained tumor-free, compared with 0% and ̴ 5% survival for vaccine and anti-PD-1 treatments alone, respectively. Cell uptake of the E2 nanoparticle in vitro was also investigated, and we demonstrated that surface display of CpG on E2 increased the nanoparticle uptake by APCs, which can potentially further increase the vaccine efficacy. Altogether, our results demonstrate the potential of the E2 protein nanoparticle as an effective cancer vaccine platform for inducing anti-tumor responses. These findings could lead to more effective cancer treatments.