246 SPECIFIC CD4+ AND CD8+ T CELLS ACTIVATION BY MULTI-PEPTIDE VACCINATION IN PATIENTS WITH STAGE III RENAL CELL CARCINOMA
2011-04-01

You have accessJournal of UrologyKidney Cancer: Basic Research1 Apr 2011246 SPECIFIC CD4+ AND CD8+ T CELLS ACTIVATION BY MULTI-PEPTIDE VACCINATION IN PATIENTS WITH STAGE III RENAL CELL CARCINOMA Jens Bedke, Karoline Laske, Cécile Gouttefangeas, Susan Feyerabend, Jörg Hennenlotter, Annemarie Dröge, Patricia Hrstic, Stefan Stevanovic, Arnulf Stenzl, and Hans-Georg Rammensee Jens BedkeJens Bedke Tuebingen, Germany More articles by this author , Karoline LaskeKaroline Laske Tuebingen, Germany More articles by this author , Cécile GouttefangeasCécile Gouttefangeas Tuebingen, Germany More articles by this author , Susan FeyerabendSusan Feyerabend Tuebingen, Germany More articles by this author , Jörg HennenlotterJörg Hennenlotter Tuebingen, Germany More articles by this author , Annemarie DrögeAnnemarie Dröge Tuebingen, Germany More articles by this author , Patricia HrsticPatricia Hrstic Tuebingen, Germany More articles by this author , Stefan StevanovicStefan Stevanovic Tuebingen, Germany More articles by this author , Arnulf StenzlArnulf Stenzl Tuebingen, Germany More articles by this author , and Hans-Georg RammenseeHans-Georg Rammensee Tuebingen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.315AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES An effective adjuvant therapy for locally advanced non metastatic renal cell carcinoma (RCC) is still matter of investigation. Specific immune therapy is a promising approach. The efficacy of a multi-peptide vaccine was investigated in an ongoing adjuvant phase I/II clinical trial in advanced or metastatic renal cell carcinoma after R0 resection. Aim was here to analyse vaccine specific T cell activation. METHODS Vaccination was performed with a peptide cocktail containing 3 to 12 HLA-class I binding peptides for CD8+ specific T cell stimulation derived from tumor associated antigens (TAA), depending on the HLA alleles expressed by the individual patient. 3 to 4 HLA class II binding peptides were also included for CD4+ T cell stimulation. The vaccine was applied either intradermally with GM-CSF as adjuvant or subcutaneously in Montanide ISA51 for 12 months or until progression. For T cell immunomonitoring, PBMC from different vaccination time points are thawed and stimulated in vitro with the vaccination peptides for 12 days. Peptide-specific CD4+ and CD8+ T cells are detected by IFN-gamma Elispot, tetramer staining (for HLA-A*02 positive patients) and intracellular multicytokine staining. RESULTS 22/40 patients have terminated the treatment so far. Up to now, we could detect a strong CD4+ T cell response in all analysed patients. CD4+ T cells essentially recognize two HLA-class II binding epitopes derived from the carbonic anhydrase 9 and the cyclin-D1 protein. In HLA-A*02 positive patients, peptides derived from the proteins cyclin-D1 and guanylate cyclase 1 were the most frequently recognized, with low frequencies of specific T cells. T cell immunomonitoring of further patients including HLA-A*02 negative individuals is ongoing. CONCLUSIONS The results indicate that in patients with low tumor burden in stage III RCC a specific CD4+ and CD8+ T cell activation can be achieved. The study is ongoing and results of a prolonged recurrence-free survival are pending. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e99 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jens Bedke Tuebingen, Germany More articles by this author Karoline Laske Tuebingen, Germany More articles by this author Cécile Gouttefangeas Tuebingen, Germany More articles by this author Susan Feyerabend Tuebingen, Germany More articles by this author Jörg Hennenlotter Tuebingen, Germany More articles by this author Annemarie Dröge Tuebingen, Germany More articles by this author Patricia Hrstic Tuebingen, Germany More articles by this author Stefan Stevanovic Tuebingen, Germany More articles by this author Arnulf Stenzl Tuebingen, Germany More articles by this author Hans-Georg Rammensee Tuebingen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...