Development of DC-based immunotherapy for treatment of HNC

Most conventional vaccines are composed of purified immunogens or their subunits, and primary elicit humoral immunity. In contrast, dendritic cells (DC) are antigen-presenting cells specialized to initiate cellular immunity, including cytotoxic T lymphocytes that kill infected or malignant target cells. For vaccination strategies, mature DC are generated from adherent blood monocytes in vitro and loaded with tumour antigen to induce protective anti- tumour immunity. Actually, more than 1000 patients around the world with different types of cancer were treated with DC-based vaccines. In pilot clinical trials of DC vaccination for patients with non-Hodgkin`s lymphoma, melanoma and renal carcinoma, induction of anti-tumour immune responses and tumour regressions have been observed. However, a potential antitumor efficiency of DC-based immunotherapy in head and neck carcinomas was not investigated yet, although a negative correlation between number of the tumour-infiltrating DC and prognosis for these tumours are well documented. Moreover, an enormous concentration of lymphoid organs within head and neck suggests that DC-based immunotherapy in this environment appears feasible. The aim of our project is the development of DC-based immunotherapy for treatment of selected head and neck tumors. First, we want to compare phagocytic and antigen presenting capacities of DC in the presence or absence of opsonins on the surface of target tumour cells. Second, the cooperation between dendritic and monocytic cells during antigen processing and presentation will be investigated. Third, we plan to apply acquired knowledge to improve the DC-mediated priming of T and B lymphocytes against head and neck carcinomas, with special focus on antigens preferentially associated with this type of tumours.