The goal was to develop immunological strategies that effectively eliminate cancer cells while mitigating the risk of immune-related adverse events (irAEs).In the first part therapies that can redirect anti-cytomegalovirus (CMV) CD8-positive T cells to selectively target and eliminate cancer cells are explores and investigated. In this respect, anti- anti-cytomegalovirus T cells hold significant promise due to their high abundance in CMV-seropositive subjects, their propensity to increase with age, and their maintenance of excellent effector functions.In the second part the focus shifts to overcoming resistance caused by cancer cell-exposed immune checkpoints. We identified a previously unknown direct inhibitory effect of CD47 on T cell-mediated elimination of cancer cells.
Additionally, the development of a novel series of bispecific antibodies was described. These antibodies selectively block immune checkpoints CD47 and CD73. They do so in a tumor-specific manner. This is achieved by directing them towards Epidermal Growth Factor Receptor (EGFR) or Epithelial Cell Adhesion Molecule (EpCAM)-overexpressing cancer cells.
Both approaches show promising results, appear to reduce side effects and may be applicable to a broader group of cancer patients who do not respond to current treatment regimens.
