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01-07-2008 | Original Article

A33 antigen displays persistent surface expression

Authors: Margaret E. Ackerman, Cecile Chalouni, Michael M. Schmidt, Vivek V. Raman, Gerd Ritter, Lloyd J. Old, Ira Mellman, K. Dane Wittrup

Published in: Cancer Immunology, Immunotherapy | Issue 7/2008

Abstract

The A33 antigen is a cell surface glycoprotein of the small intestine and colonic epithelium with homology to tight junction-associated proteins of the immunoglobulin superfamily, including CAR and JAM. Its restricted tissue localization and high level of expression have led to its use as a target in colon cancer immunotherapy. Although the antigen is also present in normal intestine, radiolabeled antibodies against A33 are selectively retained by tumors in the gut as well as in metastatic lesions for as long as 6 weeks. Accordingly, we have studied the trafficking and kinetic properties of the antigen to determine its promise in two-step, pretargeted therapies. The localization, mobility, and persistence of the antigen were investigated, and this work has demonstrated that the antigen is both highly immobile and extremely persistent—retaining its surface localization for a turnover halflife of greater than 2 days. In order to explain these unusual properties, we explored the possibility that A33 is a component of the tight junction. The simple property of surface persistence, described here, may contribute to the prolonged retention of the clinically administered antibodies, and their uncommon ability to penetrate solid tumors.

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Title: A33 antigen displays persistent surface expression
Authors: Margaret E. Ackerman
Cecile Chalouni
Michael M. Schmidt
Vivek V. Raman
Gerd Ritter
Lloyd J. Old
Ira Mellman
K. Dane Wittrup
Publication date: 01-07-2008
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 7/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0433-x

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