Tumor-derived dendritic cell vaccinations as novel approach for the prevention of cancer relapse and metastasis

90% of all cancer deaths result from the development of metastasis or relapse and treatments specifically targeting these phenomena are currently lacking. Hence, there is an urgent medical need for new treatments against cancer metastasis and tumor relapse, whereby the side effects of conventional therapies (eg chemotherapy) are avoided. In this respect, harnessing the patient’s immune system to destroy remaining cancer cells seems an attractive approach that witnessed breakthrough successes in recent years. Dendritic cells (DCs) are crucial for the generation of antitumor immune responses and constitute an essential target in efforts to generate therapeutic immunity against cancer. However, the current DC-based therapies result in durable tumor regression only in very few patients, while most patients display no clinical signs of tumor control and do not have prolonged survival, emphasizing the shortcomings as well as the potential of these therapies. We recently demonstrated the presence of strongly immunostimulatory DC populations within the tumor microenvironment of multiple mouse and human tumors, and importantly, tumor-derived cDC-based vaccinations could reduce the growth of tumors also in preclinical models that are resistant to the currently used (immuno)therapies. Hence, tumor-derived cDC vaccination strategies provide a novel therapeutic approach that overcome the currently witnessed barriers to effective therapeutic responses. This project aims to further exploit the potential of tumor-derived cDC vaccination strategies by combining them with existing immunotherapies that increase the activation status of cDCs in vivo and remodel the tumor microenvironment to induce stronger antitumor responses. These optimized tumor-derived cDC combination therapies will subsequently be used to combat the formation of metastasis and tumor relapse. The finality of the project aims to provide preclinical data for the use of tumor-derived cDC vaccination strategies as a personalized follow-up therapy, whereby genuine tumor-derived cDCs will be sorted from post-operative, resected tumor tissue and used to induce potent immune responses combating metastases and regrowth of the primary tumor