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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 12/2006

01-12-2006 | Original Article

Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma

Authors: Ying Waeckerle-Men, Edith Uetz-von Allmen, Markus Fopp, Roger von Moos, Christel Böhme, Hans-Peter Schmid, Daniel Ackermann, Thomas Cerny, Burkhard Ludewig, Marcus Groettrup, Silke Gillessen

Published in: Cancer Immunology, Immunotherapy | Issue 12/2006

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Abstract

Background: Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor antigen-specific T cell responses in cancer patients. However, tumor escape with down-regulation or complete loss of target antigens may limit the susceptibility of tumor cells to the immune attack. Concomitant generation of T cell responses against several immunodominant antigens may circumvent this potential drawback. In this trial, we determined the immunostimulatory capacity of autologous DC pulsed with multiple T cell epitopes derived from four different prostate-specific antigens in patients with advanced hormone-refractory prostate cancer. Patients and methods: Autologous DC of HLA-A*0201+ patients with hormone-refractory prostate cancer were loaded with antigenic peptides derived from prostate stem cell antigen (PSCA14–22), prostatic acid phosphatase (PAP299–307), prostate-specific membrane antigen (PSMA4–12), and prostate-specific antigen (PSA154–163). DC were intradermally applied six times at biweekly intervals followed—in the case of an enhanced immune response—by monthly booster injections. Immune monitoring during the time of ongoing vaccinations (12–59 weeks) included ex vivo ELISPOT measurements, MHC tetramer analysis and in vitro cytotoxicity assays. Results: Of the initial six patients, three qualified for long-term multi-epitope DC vaccination. This regime was tolerated well by all three patients. The vaccination elicited significant cytotoxic T cell responses against all prostate-specific antigens tested. In addition, memory T cell responses against the control peptides derived from influenza matrix protein and tetanus toxoid were efficiently boosted. Clinically, the long-term DC vaccination was associated with an increase in PSA doubling time. Conclusions: DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses.
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Metadata
Title
Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma
Authors
Ying Waeckerle-Men
Edith Uetz-von Allmen
Markus Fopp
Roger von Moos
Christel Böhme
Hans-Peter Schmid
Daniel Ackermann
Thomas Cerny
Burkhard Ludewig
Marcus Groettrup
Silke Gillessen
Publication date
01-12-2006
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 12/2006
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0157-3

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