Approximately 50% of all human colorectal tumors develop distant metastases. Surgery for metastatic disease remains the only hope for cure. Systemic therapies, including chemotherapy and EGFR- and VEGF targeting antibodies have prolonged median overall survival to approximately 2 years, but have little effect on long-term survival. Immune checkpoint inhibitors are currently being tested for their therapeutic value and are expected to improve long-term survival. Such therapies may also be effective in other subtypes, possibly as part of combination treatment strategies. Unfortunately, the immune-suppressive activity of tumor-associated Treg cells represents a major hurdle for effective antitumor immunity, but highlighting their potential as an immunotherapeutic target. For this reason, there is considerable interest in the possible synergistic opportunities of combining Treg cell-targeted therapies with other modalities, such as immune checkpoint blockade, immune agonists, tumor-specific vaccines, radiotherapy, and chemotherapy. However, increased knowledge into mechanisms underlying Treg accumulation, function, and their role in metastasis and therapy resistance needs to be gained before such approaches can be clinically tested. Rational design of such strategies in CRC requires a thorough understanding of the tumor-immune niche, and in particular the role of T regulatory (Treg) cells which is currently lacking. Here, through the isolation and characterization of CRC-associated Treg cells together with the development and application of novel organoid based in vitro model systems for studying Treg cell-tumor interactions, we will advance our understanding of the tumor-immune niche. This information can be used to test and develop novel treatment strategies against CRC tumors. A major aim of the work is to translate fundamental research results into clinically useful tools and novel therapeutic strategies.
This project is part of a collaborative venture between the labs of Prof. Paul Coffer and Prof. Onno Kranenburg at UMC Utrecht together with Genmab BV. The successful candidate will be primarily based in the Coffer Lab, part of the Center for Molecular Medicine (CMM). Over the last decade, the Coffer group has developed considerable expertise in isolating, manipulating and characterizing both murine and human Treg cells. Work in the Kranenburg group is focused on metastatic colorectal cancer, aiming to obtain insight into the metastatic process and developing anti-metastatic therapeutic strategies. Genmab is an international biotechnology company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer. The strong research experience between UMC Utrecht and Genmab BV will combined to characterize regulatory T cells in metastatic colorectal cancer (CRC). Together the combined experience in studying both immune cells and tumor biology, technologies and expertise will allow the project goals to be realized.
You have a PhD in biomedical science, affinity with immunology and molecular-cell biology, and thrive in a dynamic and multidisciplinary research environment. In addition, you are motivated, creative and hard-working, with good organization and management skills, interested to work between groups at the UMC Utrecht and Genmab BV in the development of immune-niche targeting therapeutics. This position is also supported by a full-time technician.
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