Tumor antigen-specific humoral and cellular immune response as tools for diagnostic and therapy of cancer patients
Final Report Abstract
Our project was a contribution to the characterization of the adaptive immunity in cancer patients. Aim was to identify potential tools which can be used for diagnostics (focus on antibodies) and /or for therapeutical approaches especially immunotherapy (focus on T‐cell epitopes). In the first part of the project, we demonstrated for the 1st time that hydin is a tumor‐associated antigen (more precisely two alternative splicing variants of the hydin gene) which can be targeted by cytotoxic T effector cells (and antibodies). We identified 2 T‐cell epitopes and show that spontaneous T‐cell responses occur against hydin in some cancer patients. In the second part of the project, we could show that radiofrequency ablation is able to stimulate the adaptive immune system against the patient tumor, and propose that RFA could be effectively combined to immunotherapy for the treatment of some cancer patients. Moreover, we show that two RCC‐associated proteins that we previously described are frequently recognized by natural Ab in cancer patients; further investigations are needed to determine whether antibody responses of patients undergoing immunotherapy can be valuable biomarkers of clinical course.
Publications
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Activation of CD4+ and CD8+ T cells in patients with renal cell carcinoma after multi‐peptide vaccination. 40th Annual Meeting German Society for Immunology/Deutsche Gesellschaft für Immunologie 2010
K. Laske, A. Dröge, S. Feyerabend, J. Hennenlotter, J. Bedke, P. Hrstic, S. Stevanovic, A. Stenzl, C. Gouttefangeas, H.‐G. Rammensee
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“T‐cell immunomonitoring in patients with renal cell carcinoma after multi‐peptide vaccination”. CIMT2010
K. Laske, A. Dröge, S. Feyerabend, J. Hennenlotter, J. Bedke, P. Hrstic, S. Stevanovic, A. Stenzl, C. Gouttefangeas, H.G. Rammensee
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"CIMT 2010: report on the eighth annual meeting of the Association for Cancer Immunotherapy, May 26‐28, 2010, Mainz, Germany." Cancer Immunol Immunother 60(3): 443‐450. (2011)
S. K. Singh, K. Laske, C. Gouttefangeas, C. M. Britten, M. J. Welters
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Alternative splice variants of human HYDIN gene as novel cancer‐associated antigens and identification of derived CD8 T cell epitopes. Progress In Vaccination Against Cancer PIVAC 2011, 10‐13 October 2011
K. Laske, Y. V. Shebzukhov, V. Vass, S. Walter, S. V. Khlgatian, D. V. Kuprash, S.A. Nedospasov, S. Stevanović, H.G. Rammensee, C. Gouttefangeas
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enal cell carcinoma patients exhibit vaccine‐specific CD4+ and CD8+ T cells after individual multi‐peptide vaccination. CIMT2011
K. Laske, A. Dröge, S. Feyerabend, S. Stevanović, J. Bedke, J. Hennenlotter, A. Stenzl, C. Gouttefangeas, H.G. Rammensee
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More than just tumor destruction: immunomodulation by thermal ablation of cancer. Clinical and Developmental Immunology 2011; 160250. Epub 2011 Dec 29
Haen SP, Pereira PL, Salih,HR, Rammensee HG, Gouttefangeas C
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Tumor antigen‐ specific T cells and antibodies in cancer patients treated with radiofrequency ablation. Int J Cancer 2011, 128:2653‐2662
Widenmeyer M, Shebzukhov Y, Haen SP, Schmidt D, Clasen S, Boss A, Kuprash DV, Nedospasov SA, Stenzl A, Aebert H, Wernet D, Stevanović S, Pereira PL, Rammensee HG, Gouttefangeas C
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"The development of standard samples with a defined number of antigen‐specific T cells to harmonize T cell assays: a proof‐of‐ principle study." Cancer Immunol Immunother. (2012, Sep 18. [Epub ahead of print])
S.K. Singh, B. Tummers, T.N. Schumacher, R. Gomez, K.L. Franken, E.M. Verdegaal, K. Laske, C. Gouttefangeas, C. Ottensmeier, M.J. Welters, C.M. Britten, S.H. van der Burg