title: Telomerase-pulsed dendritic cells: preclinical results and outcome of a clinical phase I/II trial in patients with metastatic renal cell carcinoma.
abstract: 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.
authors.affiliation: University of Bonn, Department of Internal Medicine I, Bonn, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Märten
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sievers
authors.forename: Peter
authors.initials: P
authors.lastname: Albers
authors.forename: Stefan
authors.initials: S
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Franchy
authors.forename: Alexander
authors.initials: A
authors.lastname: von Ruecker
authors.forename: Holger
authors.initials: H
authors.lastname: Strunk
authors.forename: Hans Heinz
authors.initials: HH
authors.lastname: Schild
authors.forename: Alexandra
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authors.lastname: Schmiedel
authors.forename: Thorsten
authors.initials: T
authors.lastname: Sommer
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
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