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PankoMab: a potent new generation anti-tumour MUC1 antibody

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Abstract

Recently, we described a new carbohydrate-induced conformational tumour-epitope on mucin-1 (MUC1) with the potential for improvement of immunotherapies [29, 30]. PankoMab is a novel antibody, which binds specifically to this epitope and was designed to show the highest glycosylation dependency and the strongest additive binding effect when compared to other MUC1 antibodies. This enables PankoMab to differentiate between tumour MUC1 and non-tumour MUC1 epitopes. It has a high-affinity towards tumour cells (e.g. K D [M] of 0.9 and 3×10−9 towards NM-D4 and ZR75-1, respectively) and detects a very large number of binding sites (e.g. 1.0 and 2.4×106 for NM-D4 and ZR75-1, respectively). PankoMab is rapidly internalised, and after toxin coupling is able to induce very effectively toxin-mediated antigen-specific tumour cell killing. PankoMab reveals a potent tumour-specific antibody-dependent cell cytotoxicity (ADCC). PankoMab is, therefore, distinguished by a combination of advantages compared to other MUC1 antibodies in clinical development, including higher tumour specificity, higher affinity, a higher number of binding sites, largely reduced binding to shed MUC1 from colon and pancreatic carcinoma patients, no binding to mononucleated cells from peripheral blood (except ~7% of activated T cells), stronger ADCC activity and rapid internalisation as required for toxin-mediated cell killing. This renders it a superior antibody for in vivo diagnostics and various immunotherapeutic approaches.

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Abbreviations

ADCC:

Antibody-dependent cell cytotoxicity

MUC1:

Mucin-1

PBMC:

Peripheral blood mononuclear cells

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Acknowledgements

We are grateful to Hans Paulsen (Hamburg, Germany) for MUC1-derived peptides, to Heinz Faulstich (Heidelberg, Germany) for the preparation of β-amanitin-antibody conjugates and for providing β-amanitin, and to Silvia von Mensdorff-Pouilly (Amsterdam, the Netherlands) for providing a standard probe for serum MUC1 detection.

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Authors and Affiliations

  1. GLYCOTOPE GmbH, Berlin, Germany

    Antje Danielczyk, Renate Stahn, Anja Löffler, Uwe Karsten & Steffen Goletz

  2. NEMOD Biotherapeutics GmbH & Co.KG, Berlin, Germany

    Renate Stahn, Dorian Faulstich & Steffen Goletz

  3. Max Delbrück Centre for Molecular Medicine, Berlin, Germany

    Uwe Karsten

  4. Department of Surgery, University of Heidelberg, Berlin, Germany

    Angela Märten

  5. Charité—Academic Medicine, Institute for Molecular Biology and Biochemistry, Humboldt University, Campus Benjamin Franklin, Berlin, Germany

    Steffen Goletz

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  1. Antje Danielczyk
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  2. Renate Stahn
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Correspondence to Steffen Goletz.

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Danielczyk, A., Stahn, R., Faulstich, D. et al. PankoMab: a potent new generation anti-tumour MUC1 antibody. Cancer Immunol Immunother 55, 1337–1347 (2006). https://doi.org/10.1007/s00262-006-0135-9

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  • DOI: https://doi.org/10.1007/s00262-006-0135-9

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