In this project we aim to develop novel targeted immunotherapy by exploiting tumor cell surface modification. The tumor cell glycocalyx can be specifically modified with azide functionalities by means of metabolic labelling. Click chemistry then allows us to attach immunomodulatory agents (e.g. Il-2 or anti-CD3 antibody) to the tumor surface. Subsequent “declick” chemistry enables detachment of these agents to elicit an enhanced cytotoxic T cell response. The fundamentals for ultrafast chemical declicking are being investigated by chemical synthesis in this subproject, along with synthesis of novel click agents. Tests on cell culture are performed by my twin-PhD Daan Smits at the Radboud UMC. Thus by metabolic reengineering and chemical functionalisation, subsequent reprogramming of the tumor microenvironment may lead to enhanced adoptive T cell therapy.