Engineering Cancer Vaccines with Ionic Liquids

Abstract

Cancer remains one of the leading causes of death worldwide, and despite advances in detection and treatment, achieving durable immune protection against recurrence remains a major challenge. Immunotherapy harnesses the body’s own immune system to recognize and eliminate cancer cells and has revolutionized cancer treatment. However, many patients fail to respond due to tumor heterogeneity and immune suppression. Cancer vaccines that utilize whole tumor cells offer a promising route to generate antitumor immunity by presenting a broad set of highly matched antigens as they use tumors as the source of antigen. Despite their rich antigen repertoire and high personalization, conventional whole tumor cell cancer vaccines have demonstrated limited clinical success due to insufficient immunogenicity. Traditional approaches, such as genetic engineering or cell surface modification, can enhance immune stimulation but are often labor-intensive, technically complex, and limited in scalability. Therefore, a simple, modular, and effective method to integrate potent immunostimulatory signals directly into whole tumor cell vaccines could substantially enhance efficacy, manufacturability, and scalability. Ionic liquids (ILs) are bulky salts comprised of organic cations and anions with a melting point below 100°C. They are highly tunable and have previously been demonstrated to have abilities in crossing biological barriers. In my dissertation research, I present a facile method to load immunostimulatory CpG oligodeoxynucleotides (ODN) into tumor cells undergoing immunogenic cell death using an ionic liquid-containing cocktail, permitting cell modification in a single step for cancer vaccination. Results indicate that these adjuvant-loaded tumor cells (called IL-Vax) enhance the uptake by dendritic cells (DCs) and their subsequent activation. IL-Vax offers strong protection against tumor growth in a prophylactic setting with 100% survival in vaccinated mice 60 days post-challenge. Furthermore, IL-Vax combined with immune checkpoint blockade leads to slowed tumor growth and a 60% increase in median survival in B16F10 melanoma tumor-bearing mice. Our strategy enables modularity to load different cargos or cargo combinations which may be conducive for additional tailoring of such vaccines and potentially other cell loading applications.