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Lessons to be learned from primary renal cell carcinomas: novel tumor antigens and HLA ligands for immunotherapy

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Abstract

The lack of sufficient well-defined tumor-associated antigens is still a drawback on the way to a cytotoxic T-lymphocyte-based immunotherapy of renal cell carcinoma (RCC). We are trying to define a larger number of such targets by a combined approach involving HLA ligand characterization by mass spectrometry and gene expression profiling by oligonucleotide microarrays. Here, we present the results of a large-scale analysis of 13 RCC specimens. We were able to identify more than 700 peptides, mostly from self-proteins without any evident tumor association. However, some HLA ligands derived from previously known tumor antigens in RCC. In addition, gene expression profiling of tumors and a set of healthy tissues revealed novel candidate RCC-associated antigens. For several of them, we were able to characterize HLA ligands after extraction from the tumor tissue. Apart from universal RCC antigens, some proteins seem to be appropriate candidates in individual patients only. This underlines the advantage of a personalized therapeutic approach. Further analyses will contribute additional HLA ligands to this repertoire of universal as well as patient-individual tumor antigens.

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Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (SFB 510 and Graduiertenkolleg 794), the European Union (LSHB-CT-2003-503231 GenomesToVaccines), and by the German Federal Ministry of Education and Research (Fö. 01KS9602) in connection with the Interdisciplinary Center of Clinical Research, Tübingen (IZKF, Project S.04.00088). We thank Lynne Yakes for critically reading the manuscript and Patricia Hrstić for perfect technical assistance.

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Authors and Affiliations

  1. Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany

    Tobias Krüger, Oliver Schoor, Claudia Lemmel, Bjoern Kraemer, Christian Reichle, Jörn Dengjel, Toni Weinschenk, Margret Müller, Hans-Georg Rammensee & Stefan Stevanović

  2. Department of Urology, University of Tübingen, Tübingen, Germany

    Jörg Hennenlotter & Arnulf Stenzl

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  1. Tobias Krüger
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  2. Oliver Schoor
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  3. Claudia Lemmel
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  11. Hans-Georg Rammensee
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  12. Stefan Stevanović
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Correspondence to Stefan Stevanović.

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Tobias Krüger and Oliver Schoor contributed equally to this work.

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Krüger, T., Schoor, O., Lemmel, C. et al. Lessons to be learned from primary renal cell carcinomas: novel tumor antigens and HLA ligands for immunotherapy. Cancer Immunol Immunother 54, 826–836 (2005). https://doi.org/10.1007/s00262-004-0650-5

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