Development of a MUC1 cancer immunotherapy using complement targeted liposomes and organoplatinum (IV) complex as an effective anticancer drug

Abstract

The development of therapeutic and preventive cancer vaccines has been on the rise in the past decade. Extensive tumor antigen libraries supply researchers with a wide variety of targets for developing cancer vaccines. Cancer vaccines aim to induce tumor regression, eradicate tumors and establish lasting antitumor memory, while avoiding adverse reactions. However, achieving this goal is hampered by the challenges of finding tumor antigens to incite an effective immune response and creating an efficient delivery system to deliver the antigen to target cells. In this thesis, we discuss how to integrate Toll Like Receptor (TLR) agonists with a MUC1 cancer vaccine to improve its effectiveness. The goal of our research was to increase drug delivery targeting efficiency by encapsulating a MUC1 immunogenic peptide within C3 liposomes. The work described herein shows that C3 liposomes were effective at targeting delivery of MUC1 antigen to Antigen Presenting Cells (APCs), which resulted in a T and B cell immune response against MUC1. Furthermore, the addition of TLR agonists to vaccine formulations boosted vaccine effectiveness, creating a more potent treatment against MUC1 expressing cancer. Another goal of this thesis research was to synthesize organoplatinum compounds. Currently, platinum-based chemotherapy drugs are a popular option for treating cancer, however, treatment is still limited by bystander toxicity. Four octahedral organoplatinum (IV) compounds, namely [Pt(CH₃)₂X₂{bipy-R₂}] (X = Br, I; bipy-R₂ = 2,2'-bipyridine, 2,2'-bipyridine-4,4'-dicarboxylic acid), have been isolated and structurally characterized by single-crystal X-ray diffraction. The anticancer potential of each compound was assessed via an in vitro MTT assay.