Abstract
Globally, cancer incidence is increasing, with 19.3 million new cases reported in 2020 and 9.96 million deaths. Immunotherapy was introduced as a new treatment and recently, neoantigens gained a lot of interest. Neoantigens are tumor-specific antigens that can increase the immune response against cancer cells. These can be induced not only by mutations, but also by post-translational modifications (PTMs), from which not much is yet known. Because neoantigens are unique to tumor cells, they are considered perfect targets for cancer treatment. However, multiple limitations still must be overcome, including the amount of neoantigens found in a tumor. Cold atmospheric plasma (CAP) is a novel cancer treatment method known to induce PTMs, immunogenic cell death, and increase immunogenicity. The novelty and objective of my project is to induce neoantigens with CAP to improve immunotherapy. I will use patient-derived organoids from head and neck cancer and pancreatic cancer. I will determine mutations and PTMs after treatment, by mass spectroscopy and sequencing. Next, I will generate a ranking of neoantigen candidates, induced due to the CAP treatment, with immunopeptidomics and in silico peptide prediction. I will test their immunogenicity in vitro through stimulation of T-cells with dendritic cells loaded with the candidate neoantigens. My project will lead to new targets for immunotherapy and lay the groundwork for combination treatments of immunotherapy and CAP.
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