gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

RAB38 represents a new target antigen for immunotherapy approaches in melanoma

Meeting Abstract

Suche in Medline nach

  • corresponding author presenting/speaker Dirk Jäger - Medizinische Onkologie, NCT, Universitätsklinikum Heidelberg, Deutschland
  • Alfred Zippelius - Klinik und Poliklinik für Onkologie, UniversitätsSpital Zürich
  • Christina Jochims - Medizinische Onkologie, NCT, Universitätsklinikum Heidelberg
  • Alexander Knuth - Klinik und Poliklinik für Onkologie, UniversitätsSpital Zürich

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP433

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Veröffentlicht: 20. März 2006

© 2006 Jäger et al.
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Target antigens for cancer vaccines are characterized by their tumor restricted expression and their immunogenicity. In melanoma, melanocyte differentiation antigens like Melan-A, tyrosinase, and gp100 have been shown to mediate anti-tumor responses in clinical vaccine trials. Effective vaccine strategies in metastatic disease need to target different antigens simultaneously, therefore new potential target antigens need to be identified and characterized. Here we report on RAB38, a novel serologically-defined melanocyte differentation antigen, that is highly restricted and abundantly expressed in normal melanocytes and melanoma tissues but not in other normal tissues or cancer types. We could demonstrate that RAB38 is highly immunogenic inducing spontaneous antibody responses in a significant proportion of melanoma patients. Antibody responses are melanoma specific, other melanocyte-destructive diseases like vitiligo were not associated with anti-RAB38 responses. Fine analysis of the spontaneous anti-RAB38 antibody response reveals a polyclonal B-cell recognition targeting various epitopes, though a dominant immunogenic region was preferentially recognized. Interestingly, our data indicate that this recognition is not stable over the course of a patient’s disease, as the dominant epitope may be modulated during it`s evolution. To evaluate potential HLA-A*0201 restricted CD8 T cell responses in cancer patients, we applied in-vitro sensitization with overlapping peptides spanning the RAB38 protein sequence and the reverse immunology approach. We identified a RAB38 peptide (nonamer) that showed a significant response after in-vitro sensitization of CD8 T cells derived from melanoma patients using ELISPOT assay. RAB38-specific T cell populations specifically recognized melanoma cell lines that express both HLA-A2 and RAB38. In-vitro digestion assays using purified proteasomes provide further evidence of natural processing of the RAB38 derived peptide. Applying tetramer technology, we identified spontanous CD8 T cell responses against this peptide in HLA-A*0201 melanoma patients. In addition to immune recognition, our data strongly indicate that the RAB38 derived peptide may be involved in initiating immune responses against RAB38. Together, our data strongly suggest that RAB38 iis a promising target antigen for immunotherapy approaches in melanoma. The newly identified HLA-A*0201 restricted epitope will be used in a clinical vaccine protocol in HLA-A2 positive patients with advanced RAB38 expressing melanoma.