gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

The differentiation antigen NY-BR-1 is a potential target for immunotherapy in breast cancer

Meeting Abstract

  • corresponding author presenting/speaker Inka Seil - NCT, Heidelberg, Deutschland
  • Claudia Frei - NCT, Heidelberg
  • Knut Engels - Universitätsklinik, Frankfurt
  • Holger Sültmann - DKFZ, Heidelberg
  • Elke Jäger - Krankenhaus Nordwest, Frankfurt
  • Kurt Zatloukal - Universität Graz, Graz, Österreich
  • Alexander Knuth - Universitätsspital, Zürich, Schweiz
  • Lloyd Old - Ludwig Institute for Cancer Research, New York, USA
  • Yao-Tseng Chen - Weill Medical College of Cornell University, New York, USA
  • Roland Stauber - Georg-Speyer-Haus, Frankfurt
  • Dirk Jäger - NCT, Heidelberg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocOP058

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dkk2006/06dkk168.shtml

Veröffentlicht: 20. März 2006

© 2006 Seil et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Cancer immunotherapy depends on the identification and functional characterization of potential immunogenic target antigens predominantly expressed by tumor cells. Here we describe the cloning, molecular characterization and expression analysis of the differentiation antigen NY-BR-1, we previously identified by SEREX (serological analysis of recombinant tumor cDNA expression libraries). The immunogenicity of NY-BR-1 was confirmed since we could detect spontanous NY-BR-1 specific humoral immune responses in several breast cancer patients. NY-BR-1 mRNA was shown to be exclusively expressed in testis, normal breast and breast tumors. Analyses of NY-BR-1 mRNA as well as protein expression levels demonstrated that NY-BR-1 was overexpressed in the majority (>70%) of breast tumors as well as metastases compared to normal tissue, as determined by qRT-PCR, cDNA microarrays and immunohistochemistry, respectively. Cloning of the full length NY-BR-1 cDNA predicted an open reading frame of 4.2 kb, encoding a protein of 1397 amino acids. Using a monoclonal antibody, NY-BR-1 was detectable as a 150 kDa protein solely in the membrane fraction of normal breast tissue and of breast cancer specimens. Confocal microscopy revealed that NY-BR-1 localizes to the cytoplasm and the plasma membrane in cell line models. Biochemical labeling and cell sorting experiments confirmed that NY-BR-1 encodes a novel membrane protein, that is detectable on the cell surface of living cells by the monoclonal antibody. Furthermore, we identified 2 NY-BR-1 derived HLA-A2 restricted epitopes. Cotransfection assays of COS-7 cells demonstrated that these epitopes are naturally processed and presented. The expression profile, the subcellular localization and the existence of two naturally processed HLA-A2 restricted CD8+ T cell epitopes now annotate NY-BR-1 as a highly attractive target antigen for antibody based therapies as well as for active immunotherapy in breast cancer.