Cancer Immunology, Immunotherapy

, Volume 56, Issue 2, pp 249–258 | Cite as

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

  • Alfred Zippelius
  • Asma Gati
  • Tammo Bartnick
  • Senta Walton
  • Bernhard Odermatt
  • Elke Jaeger
  • Reinhold Dummer
  • Mirjana Urosevic
  • Valeriy Filonenko
  • Kazuhiro Osanai
  • Holger Moch
  • Yao-Tseng Chen
  • Lloyd J. Old
  • Alexander Knuth
  • Dirk Jaeger
Original Article

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.

Keywords

RAB38/NY-MEL-1 Tumor antigen Humoral immune response SEREX B cell epitope Malignant melanoma 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Alfred Zippelius
    • 1
  • Asma Gati
    • 1
  • Tammo Bartnick
    • 1
  • Senta Walton
    • 1
  • Bernhard Odermatt
    • 2
  • Elke Jaeger
    • 3
  • Reinhold Dummer
    • 4
  • Mirjana Urosevic
    • 4
  • Valeriy Filonenko
    • 5
  • Kazuhiro Osanai
    • 6
  • Holger Moch
    • 2
  • Yao-Tseng Chen
    • 7
    • 8
  • Lloyd J. Old
    • 7
  • Alexander Knuth
    • 1
  • Dirk Jaeger
    • 1
    • 9
  1. 1.Klinik und Poliklinik für Onkologie, Departement für Innere MedizinUniversitätsSpital ZürichZürichSwitzerland
  2. 2.Departement für PathologieUniversitätsSpital ZürichZürichSwitzerland
  3. 3.II Medizinische KlinikKrankenhaus NordwestFrankfurtGermany
  4. 4.Dermatologische KlinikUniversitätsSpital ZürichZürichSwitzerland
  5. 5.Institute of Molecular Biology and Genetics, NAS of UkraineKievUkraine
  6. 6.Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
  7. 7.Ludwig Institute for Cancer ResearchNew YorkUSA
  8. 8.Weill Medical College of Cornell UniversityNew YorkUSA
  9. 9.Medizinische Onkologie NCTUniversitätsklinikum HeidelbergHeidelbergGermany

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