Preclinical Development – Biomolecular
2019 PharmSci 360
Glioblastoma multiforme (GBM) continues to be the most deadly and untreatable brain malignancy. Cancer immunotherapy is an increasingly attractive treatment option for patients who have been through the trifecta of surgery, radiation, and chemotherapy only to experience tumor recurrence. A precise and sustainable approach to cancer immunotherapy is the delivery of tumor-specific antigens, also known as neo-antigens. However, efficient delivery of neo-antigens to immune activation sites remains a major challenge in this therapeutic approach.
We have developed a synthetic high-density lipoprotein (sHDL) platform for delivery of neo-antigens. sHDL’s small size and high biocompatibility make sHDL an ideal candidate for lymphatic trafficking. Here, we have developed antigen peptide-sHDL vaccine formulations for treating GBM. We show that vaccinating GBM-bearing mice with sHDL nanodiscs co-loaded with GBM neo-antigens and CpG elicits robust neo-antigen-specific T-cell responses and delays tumor growth. We also show that anti-tumor effects were significantly enhanced when combined with anti-PD-L1 therapy.