Combined treatment of dendritoma vaccine and low-dose interleukin-2 in stage IV renal cell carcinoma patients induced clinical response: A pilot study.
Vaccination using dendritic/tumor cell hybrids represents a novel and promising cancer immunotherapy. We have developed a technology that can instantly purify the hybrids (dendritomas) from the fusion mixture of dendritic cells (DCs) and tumor cells. Our animal studies and a phase I study of stage IV melanoma patients demonstrated that dendritoma vaccination could be conducted without major toxicity and induced tumor cell-specific immunological and clinical responses. In this pilot study, ten stage IV renal cell carcinoma patients were studied. Dendritomas were made from autologous DCs and tumor cells and administered by subcutaneous injection. After initial vaccination, three escalating doses of IL-2 (3, 6, and 9 million units each) were followed within five days. This treatment regimen was tolerated well without severe adverse events directly related to the dendritoma vaccine. Most adverse events were related to IL-2 administration or pre-existing disease. Patient-specific immune responses were evaluated by flow cytometric measurement of interferon-gamma-producing T-cells before and after vaccination in response to stimulation with tumor antigens. Nine out of nine patients eligible for the analysis showed an increase of IFN-gamma-expressing CD4+ T cells after vaccination(s); while five out of eight patients eligible for the analysis showed an increase of IFN-gamma-expressing CD8+ T cells. Clinical responses were documented in 40% of the patients, three with stabilization of disease and one with a partial response documented by a reduction in tumor size. This pilot study demonstrated that dendritoma vaccines could be administered safely to patients with metastatic renal cell carcinoma, while producing both clinical and immunologic evidence of response.
Oncology Research Institute and the Cancer Treatment Center, Greenville Hospital System, Greenville, SC 29605, USA.
Yanzhang C
YC
Wei
Robert P
RP
Sticca
Jinhua
J
Li
Lillia M
LM
Holmes
Kelly E
KE
Burgin
Susan
S
Jakubchak
Hilary
H
Bouton-Verville
Jane
J
Williamson
Karen
K
Meyer
Lyndon
L
Evans
Julie
J
Martin
Joseph J
JJ
Stephenson
Steven
S
Trocha
Sam
S
Smith
Thomas E
TE
Wagner
D000368:Aged; D019496:Cancer Vaccines; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology; D003712:Dendrites / Q000276:immunology*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
D019496:Cancer Vaccines; D007376:Interleukin-2