Cancer immunotherapy, in particular novel treatment modalities, has revolutionized medicine. One encouraging strategy is based on chimeric antigen receptors (CARs) for redirecting immune effector cells (T cells or NK cells) towards surface-exposed tumour-associated antigens (TAAs). The interaction of CAR-modified immune effector cells with TAAs on tumour cells at the immunological synapse has been considered to influence the fitness and survival of those cells. Importantly, ligation of CARs to TAAs is both mandatory for inducing tumour cell killing and can lead to cell membrane transfer from targeted tumour cells to CAR-modified immune effector cells, a process termed trogocytosis.
This interdisciplinary transCampus project pools the expertise of Gilbert Fruhwirth and his group, King’s, in multi-scale imaging, with the expertise in the NK/CAR-NK immunotherapy of the group led by Achim Temme, TU Dresden. The main objective of this project will investigate the impact of trogocytosis on CAR-NK cell therapy. Secondly, the project will focus on bystander trogocytosis of other surface proteins, such as receptor tyrosine kinases and immune checkpoint ligands, which can affect CAR-NK activation/exhaustion statuses.