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Dendritic Cell-Based Vaccination in Solid Cancer

A. Stift, J. Friedl, P. Dubsky, T. Bachleitner-Hofmann, G. Schueller, T. Zontsich, T. Benkoe, K. Radelbauer, C. Brostjan, R. Jakesz, M. Gnant

From the Department of Surgery and Department of Radiology, University of Vienna Medical School, Vienna, Austria.

Address reprint requests to Stift Anton, MD, Department of Surgery, University of Vienna Medical School, Waehringer Guertel 18-20, A-1090 Vienna, Austria; email: a.stift{at}akh-wien.ac.at.

Purpose: Dendritic cell (DC)-based immunotherapy is rapidly emerging as a viable tool in cancer treatment. This approach has been used mostly in patients in the presence of defined tumor antigens such as melanoma. In this study, cancer patients with advanced disease that lacks defined tumor antigens were vaccinated with tumor lysate-pulsed DCs.

Patients and Methods: Twenty patients (pancreatic, hepatocellular, cholangiocellular, and medullary thyroid carcinoma) with stage IV disease were enrolled in the study. In 3-week intervals, freshly isolated autologous CD14 magnetic bead-selected monocytes were cultured in granulocyte-macrophage colony-stimulating factor and interleukin-4 to obtain immature DCs. These cells were pulsed with autologous tumor lysate and matured with tumor necrosis factor alpha. Mature DCs were applied into a groin lymph node, under ultrasound guidance. Adjuvant interleukin-2 (20,000 U/kg) was given subcutaneously daily, for 12 days, after each vaccination. Toxicity, tumor marker profile, immune response, and clinical response were determined.

Results: Vaccination was well tolerated. No physical signs of autoimmunity were detected. DC vaccination induced delayed-type hypersensitivity reactivity in 18 patients. Tumor marker responses were observed in eight patients. In addition, in three patients the generation of interferon gamma-positive T cells was induced during the vaccination. Objective changes in measurable lesions or tumor markers were evident in seven of 20 assessed patients. None of the patients was found to meet the criteria for partial or complete responses.

Conclusion: These data indicate that vaccination with autologous tumor-pulsed DCs generated from peripheral blood is safe and can induce tumor-specific cellular cytotoxicity. Clinical responses are achievable, even in patients with advanced disease.

Supported in part by the "Hygiene-Fonds," the "Buergermeister Fonds," and the "Kommission Onkologie" of the University of Vienna and by the Austrian National Bank.

Both A. Stift and J. Friedl contributed equally to this work.

Presented in part at the Thirty-Sixth Annual Meeting of the American Society of Clinical Oncology, New Orleans, Louisiana, May 20–23, 2000.

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