Original Article

Cancer Immunology, Immunotherapy

, Volume 56, Issue 2, pp 249-258

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

  • Alfred ZippeliusAffiliated withKlinik und Poliklinik für Onkologie, Departement für Innere Medizin, UniversitätsSpital Zürich Email author 
  • , Asma GatiAffiliated withKlinik und Poliklinik für Onkologie, Departement für Innere Medizin, UniversitätsSpital Zürich
  • , Tammo BartnickAffiliated withKlinik und Poliklinik für Onkologie, Departement für Innere Medizin, UniversitätsSpital Zürich
  • , Senta WaltonAffiliated withKlinik und Poliklinik für Onkologie, Departement für Innere Medizin, UniversitätsSpital Zürich
  • , Bernhard OdermattAffiliated withDepartement für Pathologie, UniversitätsSpital Zürich
  • , Elke JaegerAffiliated withII Medizinische Klinik, Krankenhaus Nordwest
  • , Reinhold DummerAffiliated withDermatologische Klinik, UniversitätsSpital Zürich
  • , Mirjana UrosevicAffiliated withDermatologische Klinik, UniversitätsSpital Zürich
  • , Valeriy FilonenkoAffiliated withInstitute of Molecular Biology and Genetics, NAS of Ukraine
    • , Kazuhiro OsanaiAffiliated withDepartment of Respiratory Medicine, Kanazawa Medical University
    • , Holger MochAffiliated withDepartement für Pathologie, UniversitätsSpital Zürich
    • , Yao-Tseng ChenAffiliated withLudwig Institute for Cancer ResearchWeill Medical College of Cornell University
    • , Lloyd J. OldAffiliated withLudwig Institute for Cancer Research
    • , Alexander KnuthAffiliated withKlinik und Poliklinik für Onkologie, Departement für Innere Medizin, UniversitätsSpital Zürich
    • , Dirk JaegerAffiliated withKlinik und Poliklinik für Onkologie, Departement für Innere Medizin, UniversitätsSpital ZürichMedizinische Onkologie NCT, Universitätsklinikum Heidelberg Email author 

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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.

Keywords

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