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Ruf, P.* ; Gires, O. ; Jäger, M.* ; Fellinger, K. ; Atz, J.* ; Lindhofer, H.*

Characterisation of the new EpCAM-specific antibody HO-3: Implications for trifunctional antibody immunotherapy of cancer.

Br. J. Cancer 97, 315-321 (2007)

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Open Access Green as soon as Postprint is submitted to ZB.

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Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is frequently overexpressed in a variety of carcinomas. This pan-carcinoma antigen has served as the target for a plethora of immunotherapies. Innovative therapeutic approaches include the use of trifunctional antibodies (trAbs) that recruit and activate different types of immune effector cells at the tumour site. The trAb catumaxomab has dual specificity for EpCAM and CD3. In patients with malignant ascites, catumaxomab significantly increased the paracentesis-free interval, corroborating the high efficacy of this therapeutic antibody. Here, we characterised the monoclonal antibody (mAb) HO-3, that is, the EpCAM-binding arm of catumaxomab. Peptide mapping indicated that HO-3 recognises a discontinuous epitope, having three binding sites in the extracellular region of EpCAM. Studies with glycosylation-deficient mutants showed that mAb HO-3 recognised EpCAM independently of its glycosylation status. High-affinity binding was not only detected for mAb HO-3, but also for the monovalent EpCAM-binding arm of catumaxomab with an excellent K(D) of 5.6 x 10(-10) M. Furthermore, trAb catumaxomab was at least a 1000-fold more effective in eliciting the eradication of tumour cells by effector peripheral blood mononuclear cells compared with mAb HO-3. These findings suggest the great therapeutic potential of trAbs and clearly speak in favour of EpCAM-directed cancer immunotherapies.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords EpCAM (CD326); immunotherapy; trifunctional antibodies

ISSN (print) / ISBN 0007-0920

e-ISSN 1532-1827

Journal British Journal of Cancer BJC

Quellenangaben Volume: 97, Issue: 3, Pages: 315-321

Publisher Nature Publishing Group

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CCG Molecular Oncology (AGV-KON)