Glycosylation is  the modification of macromolecules with carbohydrate structures These carbohydrate structures together make up a layer at the outside of all of our cells, which we call the glycocalyx Recently, technology has become available to very specifically introduce genetic modifications in mammalian cells In this project, we want to further develop this technology to introduce specific changes in the glycocalyx of cytotoxic T-cells (CTLs) There are strong indications that such glycocalyx-manipulations could have a strong impact on the functionality of these cells In particular, tumor-antigen specific CTLs with changed glycocalyx could become less sensitive to certain activity-suppressing lectin signals that are produced by many tumors In this project, as a translationally relevant model, we will make use of human CTLs equiped with a novel Chimeric Antigen Receptor (CAR) to target CD70-expressing tumors The project encompasses the design and implementation of a novel antigen recognition-triggered inducible gene suppression/overexpression technology, combined with the optimization and use of flow cytometrical glycan detection assays The glyco-engineered cells will then be studied in mouse models of AML and ovarium carcinoma The results will greatly expand our knowledge about the structure-function relationship of the glycocalyx of CTL/CAR-T cells The technology is likely to have a strong impact on the design of improved CTL/CAR-T cell-based treatments