Cancer Immunology, Immunotherapy

, Volume 54, Issue 5, pp 431–445

Epithelial tight junction proteins as potential antibody targets for pancarcinoma therapy

  • Sonja Offner
  • Armin Hekele
  • Ulrike Teichmann
  • Susanne Weinberger
  • Susanne Gross
  • Peter Kufer
  • Christian Itin
  • Patrick A. Baeuerle
  • Birgit Kohleisen
Original Article


Recombinant monoclonal antibodies are beginning to revolutionize cancer therapy. In combination with standard chemotherapy, high response rates have been reported with antibodies of the human IgG1 isotype for treatment of non-Hodgkin’s lymphoma and breast cancer. It is becoming apparent that targets for antibody-based therapies do not necessarily need to be absent from normal tissues but can be present there either in low copy numbers or with binding epitopes shielded from the therapeutic antibody. Here, we studied whether claudin proteins that form tight junctions in normal epithelia are still expressed on carcinoma cells and whether their extracellular domains can be recognized by antibodies. We show that mRNAs of claudins 1, 3, 4, and 7 are all expressed in different human carcinoma cell lines, while claudin 8 was selectively expressed in breast and pancreas cancer lines. Chicken polyclonal antibodies were raised against peptides contained within predicted extracellular domains of claudins 1, 3, and 4. Affinity-purified IgG fractions for claudins 3 and 4 were monospecific and bound to human breast and colon carcinoma lines, but not to a line of monocytic origin. Claudin 3 antibodies also homogeneously stained human renal cell carcinoma tissue and micrometastatic tumor cells as identified by cytokeratin staining in bone marrow biopsies of breast cancer patients. Fluorescence-activated cell sorting and immunocytochemistry indicated that claudin antibodies bound to the surface of tumor cells. By analogy to other tumor-associated antigens that are differentially accessible to antibodies on tumor vs normal tissue, we propose that certain claudin proteins have potential as targets for novel antibody-based therapies of carcinomas.


Antibody Carcinoma Claudin Gene expression Therapeutic target Tight junction 



Antibody-dependent cell-mediated cytotoxicity


Alkaline phosphatase


Complement-dependent cytotoxicity


Complementarity-determining region




Clostridium perfringens enterotoxin




Enzyme-linked immunosorbent assay


Epithelial cell adhesion molecule


Fluorescence-activated cell sorting


Fetal calf serum


High-performance liquid chromatography


Immunoglobulin G


Keyhole limpet hemocyanine


Natural killer cell


Phosphate-buffered saline


Polymerase chain reaction




Reverse transcription


Tight junction


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Sonja Offner
    • 1
  • Armin Hekele
    • 2
  • Ulrike Teichmann
    • 1
  • Susanne Weinberger
    • 1
  • Susanne Gross
    • 1
  • Peter Kufer
    • 1
  • Christian Itin
    • 1
  • Patrick A. Baeuerle
    • 1
  • Birgit Kohleisen
    • 1
  1. 1.Micromet AGMunichGermany
  2. 2.Department of Microbiology and ImmunologyUniversity of CaliforniaSan FranciscoUSA

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