Cell membrane Tumor antigens

The other well-known member of this superfamily is CEA or carcinoem-bryonic antigen. CEA is a widely used tumor marker, especially for monitoring patients with diagnosed colorectal cancer (M5). It is a high-molecular-weight (Afr 200,000, approximately) glycoprotein containing about 60% carbohydrate. In normal colonic cells and in well-differentiated colon carcinomas, the distribution of CEA is apical. However, in undifferentiated colonic tumors, CEA is present on all of the cell membrane (J3). Whether this altered subcellular localization of CEA mediates cancer spread is presently unclear. 

The monoclonal antibody BER-EP4 recognizes a cell-membrane glycoprotein consisting of two polypeptide chains (mol wt 34 kDa and 39 kDa). Its antigen is expressed on a wide variety of epithelial tumors, including small-cell undifferentiated carcinomas and neuroendocrine tumors. It is not found on nonepithelial or mesothelial tumors. 

The enzyme in cell extracts that is able to cleave most antigenic peptides is the thimet endooligopeptidase [EC 3.4.24.15 or TOP] [361]. Primarily cytosolic, this enzyme may also be expressed as a membrane-associated form [362]. TOP and neurolysin activities in melanoma cells were found in the culture medium and tumor cell membrane in addition to their cytosolic expression (Paschoalin, T. and Travassos, L.R., unpublished results). Different roles have been attributed to TOP particularly in the neuropeptide metabolism [363,364]. 

Monoclonal antibody therapy is based on the ability to target markers and bind to cell membrane antigens with great specificity. Many times the enhanced specificity demonstrated toward the tumor antigens allows normal cells to be protected against harmful effects, unlike conventional chemotherapy. There are several mechanisms by which monoclonal antibodies destroy or prevent further replication of malignant cells. Some monoclonal antibodies utilize tumor immunology and components of the host natural defense mechanism to exert their desired effect. For example, monoclonal antibodies can utilize tumor effector cells to promote tumor cell lysis or have the ability to directly modulate tumor function. 

A number of different tumor antigens have been identified on melanoma cells by the use of monoclonal antibodies in both human and murine models. Melanoma-associated antigens (MAAs) have been identified in the cellular membrane and cytoplasm of melanoma cells. GangUoside antigens have been of particular interest in the development of immunotherapy for melanoma. A large number of monoclonal antibodies to MAAs have been developed and are currently being used in clinical trials for the diagnosis and the therapy of melanoma. 

D2-40, a clone of podoplanin, is a recently developed commercially available antibody directed against the M2A antigen, a 40,000-kD sialoglycoprotein associated with germ cells and lymphatic endothelium. Chu and colleagues evaluated 53 cases of mesothelioma, 28 cases of reactive pleural tissue, 30 cases of pulmonary adenocarcinoma, 35 cases of renal cell carcinoma, 26 cases of ovarian serous carcinoma, 16 cases of invasive breast carcinoma, 11 cases of prostatic adenocarcinoma, and 7 cases of urothelial carcinoma. The authors found D2-40 expression in 51 of 53 (96%) mesotheliomas, 27 of 28 (96%) reactive pleural tissues, and 17 of 26 (65%) ovarian serous carcinomas. They did not find D2-40 in the other tumors examined. The authors also observed that the neoplastic cells immunostained in a cell membrane distribution. 

---