Immunotargeting of human cervical carcinoma xenograft expressing CA IX tumor-associated antigen by 125I-labeled M75 monoclonal antibody.
The aim of our present study was to explore a potential use of 125I-labeled murine monoclonal antibody M75 that recognizes carbonic anhydrase IX (CA IX) in the immunotargeting of human cervical carcinoma xenografts in nude mice. CA IX is a hypoxia-inducible antigen, whose expression is significantly associated with carcinomas of the uterine cervix, whereas normal cervical tissue does not express CA IX protein. M75 monoclonal antibody was labeled with 125I and used to quantify hypoxic induction of CA IX expression in vitro in HeLa human cervical carcinoma cells by immunoradiometric assay. HeLa cells showed inducible expression of CA IX in vitro by hypoxia (0.1% O2) and various hypoxia mimicking agents (Co2+, Ni2+, Mn2+, desferrioxamine, o-phenanthroline and Na2S2O4). CA IX expression was also upregulated in the centre of HeLa multicellular clusters (spheroids) corresponding to the conditions of chronic hypoxia. For the immunotargeting study, 125I-M75 was intravenously injected into immunodeficient mice bearing HeLa cervical carcinoma xenografts. Biodistribution profile showed selective and preferential accumulation of 125I-M75 mAb in CA IX expressing HeLa xenografts in comparison with control unreactive 125I-T111 antibody. Specificity was also confirmed by low uptake in CA IX negative C33A xenografts. In addition, CA IX expression in cervical carcinoma xenografts was analyzed by immunohistochemistry with M75. Detailed immunohistochemical analysis of HeLa xenograft sections revealed perinecrotically intensified expression of CA IX. These results indicate that M75 mAb, recognizing CA IX antigen, has targeting properties which could be potentially useful in radioimmunodetection or radioimmunotherapy of human cervical carcinomas and derived metastases.
Chrastina
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Institute of Virology, Slovak Academy of Sciences, 842 46 Bratislava, Slovak Republic. viruado@hotmail.com
Pastoreková
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Pastorek
J
J
D000230:Adenocarcinoma / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D007457:Iodine Radioisotopes; C475102:M75 monoclonal antibody; D009363:Neoplasm Proteins; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases