Cytokine engineering provides novel and exciting opportunities for basic science and clinical translation. In our lab, we use our insights into cytokine biogenesis and function for rational engineering approaches. Rational engineering allows us to test our hypothesis on structure formation and function of cytokines, and thus advances our understanding of  molecular principles that govern cytokine biogenesis and function. At the same time, we use engineering to make cytokines better drugs or drugs with completely novel modes of action. To achieve these goals, we combine advanced computational and experimental approaches.

As an example, we recently engineered attenuated IL-12 variants that have lower receptor binding affinities (Liebl and Aschenbrenner et al, 2023 Mol Immunol [read]). This was possible based on computational modeling combined with immunological assays. Our engineering changed the immunological signature of this cytokine, which is of utmost importance to develop IL-12 for cancer treatment without severe side-effects.

Further work in the lab focuses on completely novel designer cytokines and receptors. Engineering those will not only extend our understanding of the molecular principles that govern the formation and function of natural cytokines, but will also provide entirely new signaling circuits with highly interesting potential therapeutic applications. Such engineered systems can either be used to control immune reactions or to bio-orthogonally control engineered lymphocytes by equipping them with suitable receptors.