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Melanocyte differentiation antigen RAB38/NY-MEL-1 induces frequent antibody responses exclusively in melanoma patients

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Abstract

Expression pattern and immunogenicity are critical issues that define tumor antigens as diagnostic markers and potential targets for immunotherapy. The development of SEREX (serological analysis of recombinant expression libraries) has provided substantial progress in the identification of tumor antigens eliciting both cellular and humoral immune responses in cancer patients. By SEREX, we have previously identified RAB38/NY-MEL-1 as a melanocyte differentiation antigen that is highly expressed in normal melanocytes and melanoma tissues but not in other normal tissues or cancer types. In this study, we further demonstrate that RAB38/NY-MEL-1 is strongly immunogenic, leading to spontaneous antibody responses in a significant proportion of melanoma patients. The immune response occurs solely in malignant melanoma patients and was not detected in patients with other diseases, such as vitiligo, affecting melanocytes. Fine analysis of the spontaneous anti-RAB38/NY-MEL-1 antibody response reveals a polyclonal B cell recognition targeting various epitopes, although a dominant immunogenic region was preferentially recognized. Interestingly, our data indicate that this recognition is not rigid in the course of a patient’s response, as the dominant epitope changes during the disease evolution. Implications for the understanding of spontaneous humoral immune responses are discussed.

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Acknowledgments

This work was supported in part by a Swiss National Science Foundation special program, and a grant from the Cancer Research Institute/Ludwig Institute for Cancer Research Cancer Vaccine Collaborative, the Terry-Fox, Hanne-Liebermann and Claudia-von-Schilling Foundation, and the UBS Wealth Management. A.Z., A.G., and S.W. were supported in part by the Emmy-Noether Program (Zi685-2/3) of the Deutsche Forschungsgemeinschaft. The excellent technical assistance of Claudia Frei and Julia Karbach is greatly appreciated.

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Authors and Affiliations

  1. Klinik und Poliklinik für Onkologie, Departement für Innere Medizin, UniversitätsSpital Zürich, Rämistrasse 100, 8091, Zürich, Switzerland

    Alfred Zippelius, Asma Gati, Tammo Bartnick, Senta Walton, Alexander Knuth & Dirk Jaeger

  2. Departement für Pathologie, UniversitätsSpital Zürich, 8091, Zürich, Switzerland

    Bernhard Odermatt & Holger Moch

  3. II Medizinische Klinik, Krankenhaus Nordwest, 60488, Frankfurt, Germany

    Elke Jaeger

  4. Dermatologische Klinik, UniversitätsSpital Zürich, 8091, Zürich, Switzerland

    Reinhold Dummer & Mirjana Urosevic

  5. Institute of Molecular Biology and Genetics, NAS of Ukraine, 03143, Kiev, Ukraine

    Valeriy Filonenko

  6. Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, 920-0293, Japan

    Kazuhiro Osanai

  7. Ludwig Institute for Cancer Research, New York, NY, 10148, USA

    Yao-Tseng Chen & Lloyd J. Old

  8. Weill Medical College of Cornell University, New York, NY, 10021, USA

    Yao-Tseng Chen

  9. Medizinische Onkologie NCT, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 350, 69120, Heidelberg, Germany

    Dirk Jaeger

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  1. Alfred Zippelius
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  2. Asma Gati
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  14. Alexander Knuth
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Correspondence to Alfred Zippelius or Dirk Jaeger.

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Alfred Zippelius and Asma Gati contributed equally to this work.

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Zippelius, A., Gati, A., Bartnick, T. et al. Melanocyte differentiation antigen RAB38/NY-MEL-1 induces frequent antibody responses exclusively in melanoma patients. Cancer Immunol Immunother 56, 249–258 (2007). https://doi.org/10.1007/s00262-006-0177-z

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  • DOI: https://doi.org/10.1007/s00262-006-0177-z

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