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A33 antigen displays persistent surface expression

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

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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Acknowledgments

The authors wish to kindly acknowledge funding by NCI CA101830, and the receipt of antibodies and cell lines from the Ludwig Institute and from Dr. John Shively at City of Hope.

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Authors and Affiliations

  1. Department of Biology, Massachusetts Institute of Technology, Cambridge, USA

    Margaret E. Ackerman

  2. Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, USA

    Cecile Chalouni & Ira Mellman

  3. Department of Biological Engineering, Massachusetts Institute of Technology, Bldg E19-551, 50 Ames Street, Cambridge, MA, 02139, USA

    Michael M. Schmidt, Vivek V. Raman & K. Dane Wittrup

  4. Ludwig Institute for Cancer Research, New York Branch, Memorial Sloan-Kettering Cancer Center, New York, USA

    Gerd Ritter & Lloyd J. Old

  5. Department of Chemical Engineering, Massachusetts Institute of Technology, Bldg E19-551, 50 Ames Street, Cambridge, MA, 02139, USA

    K. Dane Wittrup

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  1. Margaret E. Ackerman
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  2. Cecile Chalouni
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  3. Michael M. Schmidt
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  4. Vivek V. Raman
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  7. Ira Mellman
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  8. K. Dane Wittrup
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Correspondence to K. Dane Wittrup.

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Ackerman, M.E., Chalouni, C., Schmidt, M.M. et al. A33 antigen displays persistent surface expression. Cancer Immunol Immunother 57, 1017–1027 (2008). https://doi.org/10.1007/s00262-007-0433-x

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  • DOI: https://doi.org/10.1007/s00262-007-0433-x

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