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[Cancer Research 63, 2127-2133, May 1, 2003]
© 2003 American Association for Cancer Research

Experimental Therapeutics

Immunological and Clinical Responses in Metastatic Renal Cancer Patients Vaccinated with Tumor RNA-transfected Dendritic Cells1

Zhen Su2, Jens Dannull2, Axel Heiser, Donna Yancey, Scott Pruitt, John Madden, Doris Coleman, Donna Niedzwiecki, Eli Gilboa and Johannes Vieweg3

Cancer Immunotherapy Program, Division of Urology, Department of Surgery [Z. S., J. D., A. H., D. Y., D. C., J. V.], Center for Cellular and Genetic Therapies, Department of Surgery [S. P., E. G.], Department of Pathology [J. M.], and Department of Biostatistics [D. N.], Duke University Medical Center, Durham, North Carolina 27710

Autologous dendritic cells transfected with total renal tumor RNA have been shown to be potent stimulators of CTLs and antitumor immunity in vitro. A Phase I trial was conducted to evaluate this strategy for feasibility, safety, and efficacy to induce tumor-specific T-cell responses in subjects with metastatic renal cell carcinoma. Renal tumor RNA-transfected dendritic cells were administered to 10 evaluable study patients with no evidence of dose-limiting toxicity or vaccine-related adverse effects including autoimmunity. In six of seven evaluable subjects, expansion of tumor-specific T cells was detected after immunization. The vaccine-induced T-cell reactivities were directed against a broad set of renal tumor-associated antigens, including telomerase reverse transcriptase, G250, and oncofetal antigen, but not against self-antigens expressed by normal renal tissues. Although most patients underwent secondary therapies after vaccination, tumor-related mortality of the study subjects was unexpectedly low with only 3 of 10 patients dying from disease after a mean follow-up of 19.8 months. These data provide a scientific rationale for continued clinical investigation of this polyvalent vaccine strategy in the treatment of metastatic renal cell carcinoma and, potentially, other cancers.




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