56INIMMUNOTHERAPY FOR HEAD AND NECK CANCER

Head and neck squamous cell carcinoma is the sixth most common cancer in the western world. Little improvement in treatment has been made over the last few decades to increase the relatively low 5-year survival rate. This calls for new treatment modalities. First, we charted the baseline levels of T cell subpopulation frequencies in these patients prior to treatment. Compared to healthy donors, a significant shift from naive to effector memory T cells was observed. A similar shift was noted in patients with oropharynx or larynx squamous cell carcinomas. The percentage of effector (memory) T cells was higher in the group of patients with HPV-positive carcinomas, suggestive of virus-induced T-cell activation. Second, HPV derived oncoproteins E6 and E7 are constitutively expressed in tumor cells and therefore are potential targets for T cell mediated adoptive immunotherapy. However, low precursor frequencies of HPV16 specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer purposes. Administration of T cell receptor transgenic T cells may form an alternative. We have isolated HPV specific TCRs and show reactivity against appropriate target cells of TCR transgenic cytotoxic and helper T cells. Third, active immunotherapy consisting of vaccination with mature dendritic cells expressing relevant tumor antigens may be explored. We have shown that survivin specific T cells can be detected ex vivo in patient derived material. Furthermore, survivin specific T cells can be induced in vitro using autologous dendritic cells with enforced expression of survivin and cytokines. However, due to fratricide killing we were unable to maintain enriched or cloned survivin specific T cells for prolonged periods of time in culture. We therefore conclude that survivin, might not be the ideal target. We will discuss options of both passive and active immunotherapy for the treatment of head and neck cancer patients and hurdles yet to overcome.