The CRC 1292 is a translational research program in targeting inefficient immunity in the context of chronic infections and cancer.
Our CRC builds on recent observations showing that inefficient immunity in cancer and in chronic infections is caused by a disequilibrium between activating and suppressive signals. In addition the innate regulatory circuits provide the major mechanisms rendering adaptive immune responses inefficient and refractory to specific activation.
Our central aim is to perform an unprecedented comparative analysis of the various immune evasion mechanisms in cancers and in chronic infections to obtain a detailed map of common and disease-specific immune escape checkpoints. That such comparative analyses across disease entities may indeed be highly promising to develop novel immunotherapeutic strategies is illustrated by the identification of the inhibitory PD-1/PD-1 ligand system as mediator of inefficient immunity in chronic viral infections which was finally exploited to address immune suppression in clinical therapy of cancer.
However, it remains a major challenge to expand such observations and to better understand to which extent common or disease-specific mechanisms contribute to immune dysfunction in cancer or chronic infections and, as an important consequence, to exploit this knowledge to develop disease-specific therapeutic strategies with reduced side effects.
The CRC 1292 will confront these central challenges by identifying common and disease-specific molecular checkpoints with the aim to develop personalized therapeutic strategies based on the combination of antigen-specific and antigen-independent strategies. So far, the incomplete understanding of the complexity of the interplay between innate and adaptive immune regulatory networks has restrained the efficacy of vaccination strategies. Targeted approaches relieving the brakes imposed by these complex circuits can be expected to have a profound impact on the efficacy of tumor and pathogen-specific immunotherapies and thereby address major health challenges of our days.