Therapeutic vaccination against metastatic renal cell carcinoma by autologous dendritic cells: preclinical results and outcome of a first clinical phase I/II trial.
In this study we have presented in vitro data and results of a preliminary clinical trial using dendritic cells (DC) in patients with progressive metastatic renal cell carcinoma. DC precursor cells were obtained from peripheral blood mononuclear cells (PBMC). DC were pulsed with autologous tumor cell lysate if available. In total, 15 patients were treated with a median of 3.95 x 10(6) DC administered and ultrasound-guided into a lymph node or into adjacent tissue. Seven patients remained with progressive disease (PD), 7 patients showed stable disease (SD), and one patient displayed a partial response (PR). Most interestingly, the patient who was treated with the highest number of DC (14.4 x 10(6) DC/vaccine) displayed a PR. Delayed-type hypersensitivity (DTH) reaction using autologous tumor lysate was positive in 3 out of 13 patients, including the patient with PR. Two out of 3 patients receiving additional treatment with keyhole limpet hemocyanin (KLH) showed reactivity to KLH after vaccination. CD3+CD4+ and CD3+CD28+ cells as well as the proliferation rate of peripheral blood lymphocytes (PBL) increased significantly in the blood of patients during therapy. In conclusion, our observations confirm the capability of tumor-lysate pulsed autologous DC vaccines to stimulate an immune response in patients with metastatic renal cell carcinoma even in the presence of a large tumor burden. The lack of adverse effects together with immunologic effects support further investigation of this novel therapeutic approach. Further studies are necessary to demonstrate clinical effectiveness in cancer patients, in particular in patients with less advanced disease.
Märten
Angela
A
Department of Internal Medicine I, University of Bonn, Sigmung Freud-Strasse 25, 53105 Bonn, Germany.
Flieger
Dimitri
D
Renoth
Sabine
S
Weineck
Silvia
S
Albers
Peter
P
Compes
Markus
M
Schöttker
Björn
B
Ziske
Carsten
C
Engelhart
Steffen
S
Hanfland
Peter
P
Krizek
Ludmila
L
Faber
Cora
C
von Ruecker
Alexander
A
Müller
Stefan
S
Sauerbruch
Tilman
T
Schmidt-Wolf
Ingo G H
IG
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014611:Vaccination
D016207:Cytokines; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin