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

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

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WAECKERLE-MEN, Ying, Edith UETZ-VON ALLMEN, Markus FOPP, Roger von MOOS, Christel BÖHME, Hans-Peter SCHMID, Daniel ACKERMANN, Thomas CERNY, Burkhard LUDEWIG, Marcus GRÖTTRUP, Silke GILLESSEN, 2006. Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma. In: Cancer Immunology, Immunotherapy. 55(12), pp. 1524-1533. ISSN 0340-7004. eISSN 1432-0851. Available under: doi: 10.1007/s00262-006-0157-3

@article{WaeckerleMen2006-12Dendr-22115, title={Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma}, year={2006}, doi={10.1007/s00262-006-0157-3}, number={12}, volume={55}, issn={0340-7004}, journal={Cancer Immunology, Immunotherapy}, pages={1524--1533}, author={Waeckerle-Men, Ying and Uetz-von Allmen, Edith and Fopp, Markus and Moos, Roger von and Böhme, Christel and Schmid, Hans-Peter and Ackermann, Daniel and Cerny, Thomas and Ludewig, Burkhard and Gröttrup, Marcus and Gillessen, Silke} }

Schmid, Hans-Peter Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate carcinoma Ludewig, Burkhard 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.<br /><br />Patients and methods:<br />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.<br /><br /><br />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.<br /><br /><br />Conclusions: DC-based multi-epitope immunotherapy with repeated boosting in men with hormonerefractory prostate carcinoma is feasible and generates efficient cellular antitumor responses. Gröttrup, Marcus Gröttrup, Marcus Gillessen, Silke 2013-02-25T12:29:48Z Fopp, Markus 2006-12 Cancer Immunology, Immunotherapy ; 55 (2006), 12. - S. 1524-1533 terms-of-use Waeckerle-Men, Ying Ludewig, Burkhard Ackermann, Daniel 2013-02-25T12:29:48Z Böhme, Christel Böhme, Christel Uetz-von Allmen, Edith Ackermann, Daniel Cerny, Thomas Moos, Roger von Waeckerle-Men, Ying Gillessen, Silke Uetz-von Allmen, Edith Fopp, Markus eng Schmid, Hans-Peter Cerny, Thomas Moos, Roger von

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