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.
Cancer Immunotherapy Program, Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Zhen
Z
Su
Jens
J
Dannull
Axel
A
Heiser
Donna
D
Yancey
Scott
S
Pruitt
John
J
Madden
Doris
D
Coleman
Donna
D
Niedzwiecki
Eli
E
Gilboa
Johannes
J
Vieweg
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