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Clinical Cancer Research Vol. 8, 3369-3376, November 2002
© 2002 American Association for Cancer Research


Clinical Trials

Immunotherapy of Metastatic Renal Cell Carcinoma with Tumor Lysate-pulsed Autologous Dendritic Cells1

Lorenz Höltl2, Claudia Zelle-Rieser2, Hubert Gander, Christine Papesh, Reinhold Ramoner, Georg Bartsch, Hermann Rogatsch, Adel L. Barsoum, Joseph H. Coggin, Jr. and Martin Thurnher3

Department of Urology (L.H., C.Z.R., H.G., C.P., R.R., G.B., M.T.) and Institute of Pathology (H.R.), University of Innsbruck, 6020 Innsbruck, Austria, and the Department of Microbiology and Immunology (J.H.C., Jr., A.L.B.), University of South Alabama, College of Medicine, Mobile, Alabama 36688-0002

Purpose: We wanted to evaluate feasibility and safety of dendritic cell-based immunotherapy in patients with metastatic renal cell carcinoma (RCC).

Experimental Design: Patients with metastatic RCC (n = 35) received vaccinations (i.v. or i.d.) of CD83+ autologous monocyte-derived dendritic cells (moDCs). MoDCs were loaded with lysate of cultured autologous or allogeneic permanent tumor cells (A-498) as well as keyhole limpet hemocyanin as control and helper antigen. Maturation of moDCs was induced by a combination of tumor necrosis factor {alpha}, interleukin 1ß, interleukin 6, and prostaglandin E2.

Results: Treatment was associated with transient flu-like symptoms. In 2 of 27 evaluable patients, any evidence of disease disappeared (complete response). In both cases, metastatic tissue had been the source of tumor antigen. One patient had an objective partial response. Seven patients had stable disease, the remaining 17 patients had progressive disease. In 11 of 11 patients evaluated, moDCs induced strong immune responses against keyhole limpet hemocyanin. In 5 of 6 patients tested, enhanced immune responses against oncofetal antigen (immature laminin receptor; OFA/LRP) could also be detected. The strongest responses against OFA/LRP were detectable in 2 patients with complete response and partial response, respectively. At the time of submission, mean follow up is 32 months and 8 patients are currently alive.

Conclusions: Our data indicate that moDC-based vaccination is well tolerated and has immunological as well as clinical effects in patients with metastatic RCC. OFA/LRP might be an attractive candidate antigen for DC-based immunotherapy of RCC.




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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
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Copyright © 2002 by the American Association for Cancer Research.