Projects in detail

The initiation of immunotherapy has opened a new era in cancer treatment, leading to a significant and sustained improvement in patient survival. Although checkpoint inhibitors are considered essential in modern oncology today, patient response rates show unexplained variations. Our IMIT project (Immuno-Monitoring of ImmunoTherapy) aims to identify and functionally investigate changes in patients receiving checkpoint inhibitors. This will help us to develop individual therapies for patients in the future by predicting the best response to the growing number of new checkpoint inhibitors.

Despite the improvement in response rates and survival in various tumor types, there is a potential risk of autoimmune side effects from T-cell infiltration, including rash, colitis, pneumonia, hepatitis and pituitary gland disease. Since there is evidence of a link between inflammation in different organs and a better response to treatment, we want to understand the pathogenesis behind these mechanisms. We have hypothesized that there may be a link between the incidence of uveitis and higher response rates in patients with metastatic melanoma. In patients with non-small cell lung cancer, we have also described another histologically dependent T-cell infiltration under immunotherapy.

The immune system is able to recognise and eliminate cancer cells, but this effector function is usually inhibited by the tumour. Although great success has been achieved with the development of immune-checkpoint inhibitors, only up to 50% of patients with metastatic melanoma respond to these therapies. It has been suggested that only patients with existing CD8+ T cells respond to PD1 blockade, so it is essential to induce a tumor-specific T cell response in patients without such pre-existing T cells. Many tumor-associated antigens (TAAs) are non-mutated "self-antigens" that are attractive vaccine targets since they can be shared by many patients. In this project we are working with other groups such as Prof. Stefan Kochanek (University of Ulm), Prof. Karl Lang (University of Essen) and Hookipa Biotech (Vienna) to investigate the feasibility of a new anti-tumour vaccine against melanoma-associated self-antigens (gp100, TRP-1, TRP-2, TYR). Preliminary data show that the immunization of tumor-bearing mice with viruses or recombinant vectors expressing TAAs can trigger potent innate and adaptive immune responses that lead to significantly delayed tumor growth and increased survival.

Foundend trough Swiss National Science Foundation (SNF): 157448