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Stimulation of Autologous Antitumor T-Cell Responses Against Medullary Thyroid Carcinoma Using Tumor Lysate-Pulsed Dendritic Cells

Department of Surgery (T.B.-H., A.S., J.F., K.R., P.D., G.S., T.B., B.N., C.B., R.J., M.G.), University of Vienna Medical School, Vienna, Austria 1090; Department of Pathophysiology (R.P.), University of Graz Medical School, Graz, Austria 8010

Address all correspondence and requests for reprints to: Professor Michael Gnant, M.D., University of Vienna Medical School, Department of Surgery, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail: . michael.gnant{at}akh-wien.ac.at

Abstract

Dendritic cells (DCs) have attracted wide interest because of their unique capacity to elicit primary and secondary antitumor responses. We have generated autologous tumor lysate-pulsed DCs from three patients with medullary thyroid carcinoma (MTC) and tested them for their ability to stimulate cytotoxic T-cell responses against autologous MTC tumor cells in vitro. The aim of our investigations was to evaluate the potential efficacy of DC-based immunotherapy in patients with MTC. DCs were generated from peripheral blood monocytes using GM-CSF and IL-4 (immature DCs) or GM-CSF, IL-4, and TNF (mature DCs). Our results indicate that mature tumor lysate-pulsed DCs are able to elicit a human leukocyte antigen class I-restricted cytotoxic T-cell response against autologous MTC tumor cells, whereas immature tumor lysate-pulsed DCs do not stimulate significant antitumor activity. We feel that our data may be relevant for future clinical trials of active immunotherapy using tumor lysate-pulsed DCs in patients with MTC who have residual or distant disease after surgical treatment. The fact that mature DCs displayed a substantially higher capacity to stimulate autologous antitumor T-cell responses than immature DCs underlines the importance of a maturation step in immunotherapy protocols based on DCs.

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