Lab of Cancer Immunology

Immune modulation and cancer: implications for novel cancer therapies

1. Cancer Immunotherapy: Harnessing the potential of anti-tumor immunity

It is increasingly appreciated that cancers are recognized by the immune system, and under some circumstances, the immune system may control or even eliminate tumors. Only recently, this concept has been reinvigorated by large clinical trials, demonstrating improved overall survival and, importantly, durable responses. This success has provided clear evidence that anti-tumor immunotherapy has broad efficacy across a diverse spectrum of malignancies owing to its potential for a large and sustained clinical benefit. Exciting perspectives to increase efficacy include combination therapies with targeted therapies and cytotoxic agents. Of particular note, both may modulate immune responses and augment host immunity. For example, selected agents increase the immunogenicity of dying cancer cells, inhibit the function of locally immuno-suppressive populations trigger DC maturation. We investigate mechanisms of anti-tumor immunity in a variety of different mouse models including immunocompetent syngeneic and genetically modified tumor models engineered to carry mutations in genes known to be involved in human cancers. These models offer the platform to experimentally perturb the tumor microenvironment, using different anti-tumor agents and provide increased information on their  immunostimulating effects, which are currently poorly defined. The aim of our research is to improve our understanding of the immuno-modulating capacities of anti-cancer therapies and pave the way for a rationale design of treatment algorithms combining anti-tumor agents with immunotherapy.

2. Development of anti-cancer strategies in early clinical trials

The focus lies on the investigation and development of treatment strategies, targets and delivery platforms in early trials in medical oncology. In collaboration with the Clinical Research Center (CCRC) at our division, we have programs ongoing to create a pipeline of agents that can move into the clinic. In translational projects, we aim at defining predictors of therapeutic responses and at understanding the mechanism of treatment responses and resistance and thereby defining potential new targets for cancer immunotherapy. The programs include cancer vaccines, immune modulatory drugs, monoclonal antibodies, and nanoparticles such as immunoliposomes. In collaboration with the Department of Radiology and Nuclear Medicine (Prof. Wild), a program is centred on radiopeptides against peptide receptors. To optimally develop novel anti-cancer agents such as immunotherapeutics we perform in-vitro assays to study how these compounds modulate human effector populations in freshly excised tumor tissue, thus faithfully mimicking the situation found in cancer patients. This program is performed in collaboration with the Department of Thoracic Surgery (Prof. Lardinois), Department of Gynecology (Prof. Heinzelmann) and Pathology (Prof. Bubendorf, Prof. Dirnhofer).