Mikkel Koed Møller Aasted
Blegdamsvej 3B, 2200 København N
The focus of my PhD project is to investigate the expression and function of aberrant glycan structures in cancer, as well as their use as targets for antibody-based immunotherapies, including CAR T cells.
Glycosylation is one of the most abundant and complex post-translational modifications and involves the covalent attachment of carbohydrate molecules (glycans) to glycoproteins and glycolipids. Accordingly, glycans play crucial roles in many biological processes, and changes in glycosylation is often associated with diseases, including cancer. In fact, aberrant glycosylation is a common trait shared by many cancers, and cancer cells often express immature and truncated glycan structures in contrast to the highly variable and complex glycans expressed by healthy cells.
In relation to cancer, I have great interest in the Tn-antigen, a truncated O-glycan consisting of a single GalNAc sugar attached to Ser/Thr of the protein backbone, as it is expressed in many tumours of epithelial origin and is associated with poor prognosis. Furthermore, my group have previously shown that induction of the Tn-antigen promotes oncogenic features in keratinocytes. As such, the Tn-antigen shows promise as a therapeutic target as it is found in several types of cancer and may be directly involved in oncogenesis. We have successfully generated multiple antibodies that recognise specific glycopeptide epitopes consisting of the Tn-antigen attached to a short peptide backbone, and I have shown that these antibodies are able to selectively direct T cells towards Tn expressing cells using the CAR T cell technology. I am currently working to refine the targeting of the Tn-antigen, as well as researching the origin of Tn expression in cancers and its functional implications.