TY - JOUR
T1 - Immunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells
AU - Su, Zhen
AU - Dannull, Jens
AU - Heiser, Axel
AU - Yancey, Donna
AU - Pruitt, Scott
AU - Madden, John
AU - Coleman, Doris
AU - Niedzwiecki, Donna
AU - Gilboa, Eli
AU - Vieweg, Johannes
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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 tumorspecific T cells was detected after immunization. The vaccine-induced T-cell reactivities were directed against a broad set of renal tumorassociated 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.
AB - 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 tumorspecific T cells was detected after immunization. The vaccine-induced T-cell reactivities were directed against a broad set of renal tumorassociated 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.
UR - http://www.scopus.com/inward/record.url?scp=0038066552&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038066552&partnerID=8YFLogxK
M3 - Article
C2 - 12727829
AN - SCOPUS:0038066552
VL - 63
SP - 2127
EP - 2133
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 9
ER -