Petra Keikavoussi
University of Würzburg
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Publication
Featured researches published by Petra Keikavoussi.
Journal of Immunological Methods | 1999
Beatrice Thurner; Claudia Röder; Detlef Dieckmann; Marion Heuer; Monika Kruse; Anke Glaser; Petra Keikavoussi; Eckhart Kämpgen; Armin Bender; Gerold Schuler
Dendritic Cell (DC)-based vaccination approaches in man require a reproducible DC generation method that can be performed in conformity with GMP (Good Manufacturing Practice) guidelines and that circumvents the need for multiple blood drawings to generate DC. To this end we modified our previously described method to generate mature DC from CD14 + monocytes by a two step method (priming in GM-SF + IL-4 followed by maturation in monocyte conditioned medium) for use with leukapheresis products as a starting population. Several adaptations were necessary. We established, for example, a modified adherence step to reliably enrich CD14 + DC precursors from apheresis mononuclear cells. The addition of GM-CSF + IL-4 at the onset of culture proved disadvantageous and was, therefore, delayed for 24 h. DC development from apheresis cells occurred faster than from fresh blood or buffy coat, and was complete after 7 days. Monocyte conditioned medium when added on day 6 resulted in fully mature and stable DC (veiled, highly migratory and T cell sensitizing cells with a characteristic phenotype such as 85% CD83 + , p55/fascin + , CD115/M-CSF-R - , CD86 + ) already after 24 h. The mature DC progeny were shown to remain stable and viable if cultured for another 1-2 days in the absence of cytokines, and to be resistant to inhibitory effects of IL-10. Freezing conditions were established to generate DC from frozen aliquots of PBMC or to freeze mature DC themselves for later use. The approach yields large numbers of standardized DC (5-10 x 10(8) mature CD83 + DC/leukapheresis) that are suitable for performing sound DC-based vaccination trials that can be compared with each other.
Journal of Immunology | 2000
Beatrice Schuler-Thurner; Detlef Dieckmann; Petra Keikavoussi; Armin Bender; Christian Maczek; Helmut Jonuleit; Claudia Röder; Ina Haendle; Waltraud Leisgang; Rod Dunbar; Vincenzo Cerundolo; Peter von den Driesch; Jürgen Knop; Eva B. Bröcker; Alexander H. Enk; Eckhart Kämpgen; Gerold Schuler
Dendritic cell (DC) vaccination, albeit still in an early stage, is a promising strategy to induce immunity to cancer. We explored whether DC can expand Ag-specific CD8+ T cells even in far-advanced stage IV melanoma patients. We found that three to five biweekly vaccinations of mature, monocyte-derived DC (three vaccinations of 6 × 106 s.c. followed by two i.v. ones of 6 and 12 × 106, respectively) pulsed with Mage-3A2.1 tumor and influenza matrix A2.1-positive control peptides as well as the recall Ag tetanus toxoid (in three of eight patients) generated in all eight patients Ag-specific effector CD8+ T cells that were detectable in blood directly ex vivo. This is the first time that active, melanoma peptide-specific, IFN-γ-producing, effector CD8+ T cells have been reliably observed in patients vaccinated with melanoma Ags. Therefore, our DC vaccination strategy performs an adjuvant role and encourages further optimization of this new immunization approach.
British Journal of Cancer | 2005
Selma Ugurel; Ralf Hildenbrand; A Zimpfer; P La Rosée; Peter Paschka; Antje Sucker; Petra Keikavoussi; Jürgen C. Becker; Werner Rittgen; Andreas Hochhaus; Dirk Schadendorf
This two-centre phase-II trial aimed at investigating the efficacy of imatinib in metastasised melanoma patients in correlation to the tumour expression profile of the imatinib targets c-kit and platelet-derived growth factor receptor (PDGF-R). The primary study end point was objective response according to RECIST, secondary end points were safety, overall and progression-free survival. In all, 18 patients with treatment-refractory advanced melanoma received imatinib 800 mg day−1. In 16 evaluable patients no objective responses could be observed. The median overall survival was 3.9 months, the median time to progression was 1.9 months. Tumour biopsy specimens were obtained from 12 patients prior to imatinib therapy and analysed for c-kit, PDGF-Rα and -Rβ expression by immunohistochemistry. In four cases, cell lines established from these tumour specimens were tested for the antiproliferative effects of imatinib and for functional mutations of genes encoding the imatinib target molecules. The tumour specimens stained positive for CD117/c-kit in nine out of 12 cases (75%), for PDGF-Rα in seven out of 12 cases (58%) and for PDGF-Rβ in eight out of 12 cases (67%). The melanoma cell lines showed a heterogenous expression of the imatinib target molecules without functional mutations in the corresponding amino-acid sequences. In vitro imatinib treatment of the cell lines showed no antiproliferative effect. In conclusion, this study did not reveal an efficacy of imatinib in advanced metastatic melanoma, regardless of the expression pattern of the imatinib target molecules c-kit and PDGF-R.
International Journal of Cancer | 2001
Mads Hald Andersen; Petra Keikavoussi; Eva-B. Bröcker; Beatrice Schuler-Thurner; Merete Jonassen; Ib Søndergaard; Per thor Straten; Jürgen C. Becker; Eckhart Kämpgen
Two HLA‐A2‐positive patients with advanced stage IV melanoma were treated with monocyte‐derived dendritic cells (DC) pulsed with either tumor peptide antigens from gp100, MART‐1 and MAGE‐3 alone or in combination with autologous oncolysates. Clinically, the rapid progression of disease was substantially stalled and both patients were alive for more than 15 months after initiation of therapy. Specific CTL reactivity against several tumor antigens was detectable in peripheral blood, which declined just before reactivation of disease progression. Furthermore, CD3 ζ‐chain expression detected by Western lotting was decreased in PBL at this time. In summary, our data confirm that DC‐based vaccinations induce peptide‐specific T cells in the peripheral blood of advanced‐stage melanoma patients. Although successful induction of systemic tumor antigen‐specific CTL may not lead to objective clinical tumor regression, their presence are indicative of a prolonged survival.
Journal Der Deutschen Dermatologischen Gesellschaft | 2008
Anke Hartmann; Christina Bedenk; Petra Keikavoussi; Jürgen C. Becker; Henning Hamm; Eva-Bettina Bröcker
Background: It is unclear if differences between melanoma‐associated hypopigmentation (MAH) and classical vitiligo exist.
Acta Dermato-venereologica | 2014
Anke Hartmann; Lisa Löhberg; Petra Keikavoussi; Saskia Eichner; Gerold Schuler
Fig. S3. A 38-year-old patient; A: abdominal region and shins before treatment; B: After 9 months treatment, repigmentation on the abdominal region just on the UVB-treated side, whereas better response on the legs was seen on the right, tacrolimus-treated side. Note mixture of follicular and interfollicular repigmentation on the abdominal side and follicular repigmentation on both shins. (We thank Mrs. Christine Reich and Mr. Stefan Schnetz for performing digital photography.)
Journal of Experimental Medicine | 1999
Beatrice Thurner; Ina Haendle; Claudia Röder; Detlef Dieckmann; Petra Keikavoussi; Helmut Jonuleit; Armin Bender; Christian Maczek; Doris Schreiner; Peter von den Driesch; Eva B. Bröcker; Ralph M. Steinman; Alexander H. Enk; Eckhart Kämpgen; Gerold Schuler
Annals of Oncology | 2006
Dirk Schadendorf; Selma Ugurel; Beatrice Schuler-Thurner; F. O. Nestle; Alexander H. Enk; Eva-Bettina Bröcker; Stephan Grabbe; Werner Rittgen; L. Edler; Antje Sucker; Zimpfer-Rechner C; Thomas Berger; J. Kamarashev; Günter Burg; Helmut Jonuleit; A. Tüttenberg; Jürgen C. Becker; Petra Keikavoussi; Eckhart Kämpgen; Gerold Schuler
Cancer Immunology, Immunotherapy | 2006
Marion Wobser; Petra Keikavoussi; Volker Kunzmann; Markus Weininger; Mads Hald Andersen; Juergen C. Becker
Vaccine | 2005
Kerstin Otto; Mads Hald Andersen; Andreas O. Eggert; Petra Keikavoussi; Lars Østergaard Pedersen; Jörg C. Rath; Markus Böck; Eva-B. Bröcker; Per thor Straten; Eckhart Kämpgen; Jürgen C. Becker