Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells.
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.
Su
Zhen
Z
Cancer Immunotherapy Program, Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Dannull
Jens
J
Heiser
Axel
A
Yancey
Donna
D
Pruitt
Scott
S
Madden
John
J
Coleman
Doris
D
Niedzwiecki
Donna
D
Gilboa
Eli
E
Vieweg
Johannes
J
D019496:Cancer Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D012334:RNA, Neoplasm / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019098:Telomerase / Q000276:immunology; D014162:Transfection
D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm; D019098:Telomerase