1. ¹University Department of Surgery, Royal Free and University College London Medical School, Pond St, London NW3 2XA, UK
2. ²Trion Research GmbH, Am Klopferspitz 19 D-82152, Martinsried, Germany
3. ³Trion Pharma GmbH, Frankfurter Ring 193a D-80807, Munich, Germany

Correspondence: Dr MA Chaudry, E-mail: asifchaudry@doctors.net.uk

Received 17 July 2006; Revised 9 October 2006; Accepted 3 November 2006; Published online 27 February 2007.

Abstract

Despite advances in surgery and adjuvant regimes, gastrointestinal malignancy remains a major cause of neoplastic mortality. Immunotherapy is an emerging and now successful treatment modality for numerous cancers that relies on the manipulation of the immune system and its effector functions to eradicate tumour cells. The discovery that the pan-epithelial homotypic cell adhesion molecule EpCAM is differentially expressed on gastrointestinal tumours has made this a viable target for immunotherapy. Clinical trials using naked anti EpCAM antibody, immunoconjugates, anti-idiotypic and dendritic cell vaccines have met variable success. The murine IgG2a Edrecolomab was shown to reduce mortality and morbidity at a level slightly lower than treatment with 5FU and Levamisole when administered to patients with advanced colorectal carcinoma in a large randomised controlled trial. Fully human and trifunctional antibodies that specifically recruit CD3-positive lymphocytes are now being tested clinically in the treatment of minimal residual disease and ascites. Although clinical trials are in their infancy, the future may bring forth an EpCAM mediated approach for the effective activation and harnessing of the immune system to destroy a pathological aberrance that has otherwise largely escaped its attention.