Phase I/II Trial of Dendritic Cells Pulsed with Telomerase.

Human telomerase reverse transcriptase (hTERT) could be a potential target for immunotherapy in cancer patients because it is detectable in more than 85% of human tumors including renal cell carcinoma. Here, we present results of a clinical phase I/II trial using dendritic cells (DC) pulsed with hTERT-peptides in patients with progressive metastatic renal cell carcinoma. Patients received injections of hTert-peptides pulsed autologous DC intradermally and intratumorally. DC were generated from leukapheresis products and matured by addition of a cytokine cocktail. Beside toxicity and feasibility aspects, a complex immune monitoring was a major point of interest in this study. All ten patients were in progressive disease when entering the protocol. The dendritic cell vaccine was well tolerated, no toxicity was observed. Two patients showed a mixed response (MR) and one patient a stable disease (SD). Seven out of ten patients remained in progression. Clinical outcome was based on a comparison of CT scans before and after treatment, i.e. three months after entering the protocol. 2/8 patients showed DTH reactivity after vaccination. Interestingly, there was a significant increase in cytotoxic activity of effector cells from all responders (SD and MR patients) after the first vaccination. In most cases, effector cells of responders showed cytotoxic activity in contrast to those of non-responders. Most interestingly, all non-responders had shown no cytotoxic activity before treatment. In contrast, responders showed cytotoxic activity already before start of therapy. Therefore, cytotoxic activity might be used as a predictive marker in the future. With tetramer staining, we could detect higher amounts of tumor specific cytotoxic cells in responding patients compared to non-responders. Responders possessed increasing amounts of IFN-gamma producing immunological effector cells, tested by ELISpot assay. In summary, telomerase-pulsed DC could induce a tumor-specific immune response against renal cell carcinoma.