We aim to make CAR-T cell therapy safer and more effective. We will improve CAR receptors in such a way that they can be turned on or off with approved, orally bioavailable medicines. To do this, we will rationally design protein pairs that react to the respective small molecule and insert them into established receptors. We focus on medicines suitable for clinical use and base the newly developed sensors on natural human proteins with a minimum of mutations to reduce the likelihood of immune responses to them. By optimizing the affinities of the protein pairs and placing them into the receptor on the extracellular side, we strive to increase the speed at which the receptors can be turned on or off.
Better use of the immune system in cancer therapy is an important goal of current research. One possibility is to equip T cells with a modified receptor (Chimeric Antigen Receptor; CAR) with which the cells can specifically recognize and kill cancer cells. However, this only works for a few forms of cancer and often results in severe side effects. Controlling CAR-T cells with small molecules is therefore heavily investigated but has so far mostly required receptor domains or drugs that are unsuitable for clinical use.
