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Radioiodinated humanized monoclonal antibody A33.


Chopra A.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2007 Sep 16 [updated 2007 Oct 22].


The A33 cell-surface differentiation antigen is a glycoprotein that belongs to the immunoglobulin superfamily (1). This antigen is expressed in >95% of primary and metastatic colon cancer cells, but is absent in most normal and tumor cell types (2, 3). Although the exact function of this glycoprotein is unknown, antibodies developed against the A33 antigen bind to tumor cells and exhibit prolonged retention in the tumor tissue (4). The A33 antigen was considered an important target of a mouse monoclonal antibody (mAb) developed for the treatment of colorectal cancers; the radiolabeled mAb was detectable in the tumor tissue up to 6 weeks after administration, but it was cleared from normal tissue within a week (4, 5). Radioimmunotherapy studies in a nude mouse model also showed that the antitumor effects of the A33 antigen mAb were enhanced by combination with chemotherapeutic agents (6, 7). However, patients treated with the radioiodinated murine mAb A33 showed minimal gut toxicity but developed a human anti-mouse antibody (HAMA) response after the first treatment (8). On re-treatment, the radiolabeled antibody was rapidly cleared from the blood circulation of these patients, and on imaging the label was observed to have accumulated in the liver, spleen, or adrenals, but not at the tumor sites (8). To reduce immunogenicity of the murine mAb, a humanized version of the A33 antibody (huA33) was constructed and is under evaluation in various clinical trials (9-12). Recently huA33 was labeled with radioactive astatine (211At) or lutetium (177Lu) and studied for specificity, biodistribution, and tumor targeting in rodents (13, 14). From these studies it was concluded that the labeled antibody could be used for radioimmunotherapy of colorectal cancer.

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