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SFB 1479:  Oncogene-driven immune escape (OncoEscape)

Subject Area Medicine
Biology
Term since 2021
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 441891347
 
The last five years have witnessed an explosion of research in the fields of molecular therapies and immunotherapy against cancer. Combining these fundamentally different approaches has much appeal. Approved cancer therapies that rely on a combination of molecular therapies and immunotherapy are still few in number, but this is an intensive area of research. The CRC has been at the forefront of activities aimed at combining the targeting of molecular vulnerabilities and immunotherapy for selected cancer entities. Specific focus is given to oncogenic mutations that cause abnormal signal transduction, collectively termed "oncogenic signalling". Oncogenic signalling can result from inactivation of tumour suppressor genes or from activating mutations in genes encoding oncogenic kinases. Therapeutic strategies that target oncogenic signalling in combination with cancer immunotherapy have been translated from preclinical studies into early clinical trials, such as the combination of MDM2 inhibition and adoptive T-cell transfer for acute myeloid leukaemia (AML). For the second funding period (FP2), we aim to increase our understanding of the oncogene-induced tumour cell–immune cell interactions and signals that instruct the development of an immunosuppressive tumour microenvironment by introducing novel spatial genomic, metabolomic and proteomic tools. Additionally, we will focus on translating previous results of the consortium into the human context using humanized animal models, organoids, multi-dimensional single-cell technologies and samples from cancer patient cohorts. We have recruited new group leaders that provide novel cutting-edge technologies such as CRISPR/Cas9 technology for systemic perturbation of transcription factors that mediate downstream effects of oncogenic pathway activation. We have acquired the novel technology ZMAN-seq into CRC. ZMAN-seq records transcriptomic dynamics over time by introducing time stamps into circulating immune cells and tracking them in tumour tissues. We have introduced full-spectrum flow cytometry and spatial single-cell technologies with sophisticated computation, respectively. These novel technologies and the PIs’ expertise will allow us to intensify our research on the impact that oncogenic signalling has on innate and adaptive immune cell function in the tumour microenvironment. The long-term goal of the OncoEscape consortium is to enable the transfer of knowledge obtained from basic research in preclinical models to novel cancer therapies that benefit patients. The first funding period saw the transfer of the CRC’s basic research findings into phase-I trials for selected tumour entities (e.g. NCT05447663, NCT04623216, EudraCT2021-002073-26), showing that clinical translation is feasible if a strong scientific rationale exists.
DFG Programme Collaborative Research Centres
International Connection Switzerland

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Applicant Institution Albert-Ludwigs-Universität Freiburg
 
 

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