Telomerase-pulsed dendritic cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma.
OBJECTIVE
Therapeutic vaccination with dendritic cells (DC) showed promising results in first clinical trials in cases of metastatic renal cell carcinoma (RCC). Human telomerase reverse transcriptase (hTERT) could be a potential target because it is detectable in more than 85% of human tumors including RCC.


METHODS
10 patients with progressive metastatic RCC were enrolled in a clinical phase I/II trial using DC pulsed with hTERT-peptide. Beside toxicity and feasibility aspects, a complex immune monitoring including in vitro data were evaluated. In addition to detection of tumor-specific effector cells we investigated their functionality like IFN-gamma secretion and cytotoxic activity against tumor cells.


RESULTS
The vaccine was well tolerated. Two patients showed a mixed response (MR) and one patient a stable disease (SD). Interestingly, responders showed cytotoxic activity already before start of therapy and there was a significant increase in cytotoxic activity of effector cells from all responders (SD and MR patients) after the first vaccination. In contrast non-responders showed no cytotoxic activity before and during treatment. Therefore, cytotoxic activity might be used as a predictive marker in the future. Tetramer staining detected higher amounts of tumor-specific cytotoxic cells in responding patients compared to non-responders. Also, responders possessed increasing amounts of IFN-gamma producing immunological effector cells.


CONCLUSIONS
Telomerase-pulsed DC could enhance a tumor-specific immune response against RCC.
Märten
Angela
A
University of Bonn, Department of Internal Medicine I, Bonn, Germany.
Sievers
Elisabeth
E
Albers
Peter
P
Müller
Stefan
S
Franchy
Christian
C
von Ruecker
Alexander
A
Strunk
Holger
H
Schild
Hans Heinz
HH
Schmiedel
Alexandra
A
Sommer
Thorsten
T
Sauerbruch
Tilman
T
Schmidt-Wolf
Ingo G H
IG
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