Development and Characterization of Dendritic Cell-Targeted Polymers for Cancer Immunotherapy

Abstract

Cancer vaccines and immunomodulators such as STING agonists hold great promise as cancer therapeutics but face many delivery challenges. In this work, we used polymers to deliver peptide antigens and STING agonists to dendritic cells to enhance therapeutic outcomes while minimizing off-target toxicity. In Chapter 1, we discussed key aspects in designing effective peptide-based cancer vaccines. In Chapter 2, we developed a mannosylated polymer platform to facilitate peptide antigen delivery to the lymph nodes and dendritic cells. In Chapter 3, we incorporated a lytic peptide ᴅ-melittin to the cancer vaccine platform to enhance cross- presentation and activation of antigen-specific CD8+ T cells. In Chapter 4, we report a mannosylated STING agonist drugamer platform to deliver STING agonists to dendritic cells while minimizing toxicity. In Chapter 5, we generated structurally different STING agonist drugamer platforms and combined with cancer vaccines to enhance antitumor immunity. In Chapter 6, I discussed the use of a fibronectin-binding peptide in cancer immunotherapy and proposed future directions.