Carcinoembryonic Antigen as a Target Cancer Antigen for Radiolabeled Antibodies: Prospects for Cancer Imaging and Therapy

Abstract

This paper reviews the development of cancer imaging with radiolabeled antibodies to carcinoembryonic antigen and the current status and challenges for cancer therapy with radiolabeled antibodies. Advances in antibody preparations, choice of isotope and labeling methods, as well as imaging methods have resulted in rapid and sensitive radioimmunodetection agents that can affect the management of cancer patients. Radioimmunotherapy faces other problems, but advances in antibody engineering and control of dose-limiting myelotoxicity may result in reproducible clinical responses similar to the encouraging results being obtained in the radioimmunotherapy of lymphomas.

The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily

“…Although several other mAbs capable of recognizing determinants on colon cancer cells exist (29)(30)(31)(32)(33)(34)(35), none of them matches the restricted tissue specificity of the A33 mAb. Ep-CAM (epithelial cell adhesion molecule) is a cell adhesion molecule expressed by most simple epithelia, and its expression is maintained by a large proportion of colorectal, breast, lung, pancreatic, and gastric tumors (29).…”

“…30) and recently chimeric and single-chain versions of two of them, 17-1A and 323͞A3, were developed and evaluated in cell-killing experiments (31,32). Similarly, members of the carcinoembryonic antigen family (33,34) and the pancarcinoma antigen, TAG-72 (35), have attracted attention as suitable targets for immunotherapy of colorectal, breast, and lung tumors. Though their relatively wide expression offers the opportunity to develop antibodies that can target multiple tumors, experience suggests that optimal localization of antibody to tumors may be impeded by the presence of antigen in a variety of normal tissues as well as by the presence of shed antigen in the circulation.…”

Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins

“…These soluble receptors are still capable of binding ligands or antibodies, targeting the latter in the circulation, resulting in the need for higher doses, as indicated for CEA and EGFR. 44 , 147 In addition to occurring as soluble proteins, extracellular membrane proteins are also present in the circulation on membrane particles called microvesicles ( Fig. 4 ).…”

Engineered antibodies for molecular imaging of cancer

“…Conventional wisdom holds that circulating antigen precludes effective targeting of tumor tissues, but as noted above, results in individual systems may vary and there are frequent exceptions to every rule. For example, CEA, which can be present at 10’s to 100’s of nanograms/ml in patients’ serum (or even higher in cases of medullary thyroid carcinoma), does not prevent targeting and imaging using radiolabeled anti-CEA fragments [14, 15]. Mucins, frequently bearing distinctive tumor-associated variations in glycosylation, can be present at even higher concentrations in the circulation of ovarian and breast cancer patients, yet are still viable targets for antibody-directed therapies and imaging.…”