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. 1999 Oct;81(4):741–746. doi: 10.1038/sj.bjc.6690757

MN/CA IX/G250 as a potential target for immunotherapy of renal cell carcinomas

H Uemura 1, Y Nakagawa 1, K Yoshida 1, S Saga 2, K Yoshikawa 2, Y Hirao 1, E Oosterwijk 3
PMCID: PMC2362900  PMID: 10574265

Abstract

The monoclonal antibody G250 (mAbG250) raised against a human renal cell carcinoma (RCC) has been shown to react with a large number of RCCs. Recently, G250 antigen was isolated and found to be homologous to the MN/CA9 gene originally identified in HeLa cells. To determine whether G250 antigen (MN/CA IX/G250) could be a potential therapeutic target and a tumour marker, a total of 147 cases of RCC were investigated immunohistochemically as well as by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. In addition, total RNAs extracted from patients' peripheral blood samples were analysed for MN/CA9/G250 mRNA signals. Immunohistochemistry demonstrated strong expression in 128/147 (87.1%) of RCCs, in contrast to the lack of expression observed in normal tissues. RT-PCR analyses of frozen specimens resulted in the clear detection of MN/CA9/G250 mRNA signals in 137/147 (93.2%), and despite subtle differences the results were almost identical to those for immunohistochemistry. Although high-grade and -stage tumours exhibited significantly lower expression than low-grade and -stage tumours, a large proportion of tumours expressed MN/G250 protein as well as mRNA. RT-PCR analysis of patients' blood samples revealed the presence of circulating MN/CA9/G250 expressing cells. These findings suggest that this antigen may be a potential therapeutic target as well as diagnostic marker for RCCs. © 1999 Cancer Research Campaign

Keywords: renal cell carcinoma, MN/CA IX/G250 antigen, MN/CA9/G250 gene, RT-PCR, marker

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Selected References

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  1. Brewer C. A., Liao S. Y., Wilczynski S. P., Pastorekova S., Pastorek J., Zavada J., Kurosaki T., Manetta A., Berman M. L., DiSaia P. J. A study of biomarkers in cervical carcinoma and clinical correlation of the novel biomarker MN. Gynecol Oncol. 1996 Dec;63(3):337–344. doi: 10.1006/gyno.1996.0333. [DOI] [PubMed] [Google Scholar]
  2. Hamdy F. C., Lawry J., Anderson J. B., Parsons M. A., Rees R. C., Williams J. L. Circulating prostate specific antigen-positive cells correlate with metastatic prostate cancer. Br J Urol. 1992 Apr;69(4):392–396. doi: 10.1111/j.1464-410x.1992.tb15566.x. [DOI] [PubMed] [Google Scholar]
  3. Ignatoff J. M., Oefelein M. G., Watkin W., Chmiel J. S., Kaul K. L. Prostate specific antigen reverse transcriptase-polymerase chain reaction assay in preoperative staging of prostate cancer. J Urol. 1997 Nov;158(5):1870–1875. doi: 10.1016/s0022-5347(01)64150-8. [DOI] [PubMed] [Google Scholar]
  4. Ivanov S. V., Kuzmin I., Wei M. H., Pack S., Geil L., Johnson B. E., Stanbridge E. J., Lerman M. I. Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12596–12601. doi: 10.1073/pnas.95.21.12596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Liao S. Y., Aurelio O. N., Jan K., Zavada J., Stanbridge E. J. Identification of the MN/CA9 protein as a reliable diagnostic biomarker of clear cell carcinoma of the kidney. Cancer Res. 1997 Jul 15;57(14):2827–2831. [PubMed] [Google Scholar]
  6. Liao S. Y., Brewer C., Závada J., Pastorek J., Pastorekova S., Manetta A., Berman M. L., DiSaia P. J., Stanbridge E. J. Identification of the MN antigen as a diagnostic biomarker of cervical intraepithelial squamous and glandular neoplasia and cervical carcinomas. Am J Pathol. 1994 Sep;145(3):598–609. [PMC free article] [PubMed] [Google Scholar]
  7. McKiernan J. M., Buttyan R., Bander N. H., Stifelman M. D., Katz A. E., Chen M. W., Olsson C. A., Sawczuk I. S. Expression of the tumor-associated gene MN: a potential biomarker for human renal cell carcinoma. Cancer Res. 1997 Jun 15;57(12):2362–2365. [PubMed] [Google Scholar]
  8. Oosterwijk E., Bander N. H., Divgi C. R., Welt S., Wakka J. C., Finn R. D., Carswell E. A., Larson S. M., Warnaar S. O., Fleuren G. J. Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. J Clin Oncol. 1993 Apr;11(4):738–750. doi: 10.1200/JCO.1993.11.4.738. [DOI] [PubMed] [Google Scholar]
  9. Oosterwijk E., Ruiter D. J., Wakka J. C., Huiskens-van der Meij J. W., Jonas U., Fleuren G. J., Zwartendijk J., Hoedemaeker P., Warnaar S. O. Immunohistochemical analysis of monoclonal antibodies to renal antigens. Application in the diagnosis of renal cell carcinoma. Am J Pathol. 1986 May;123(2):301–309. [PMC free article] [PubMed] [Google Scholar]
  10. Opavský R., Pastoreková S., Zelník V., Gibadulinová A., Stanbridge E. J., Závada J., Kettmann R., Pastorek J. Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships. Genomics. 1996 May 1;33(3):480–487. doi: 10.1006/geno.1996.0223. [DOI] [PubMed] [Google Scholar]
  11. Pastorek J., Pastoreková S., Callebaut I., Mornon J. P., Zelník V., Opavský R., Zat'ovicová M., Liao S., Portetelle D., Stanbridge E. J. Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. Oncogene. 1994 Oct;9(10):2877–2888. [PubMed] [Google Scholar]
  12. Pastoreková S., Parkkila S., Parkkila A. K., Opavský R., Zelník V., Saarnio J., Pastorek J. Carbonic anhydrase IX, MN/CA IX: analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts. Gastroenterology. 1997 Feb;112(2):398–408. doi: 10.1053/gast.1997.v112.pm9024293. [DOI] [PubMed] [Google Scholar]
  13. Ritchie A. W., deKernion J. B. The natural history and clinical features of renal carcinoma. Semin Nephrol. 1987 Jun;7(2):131–139. [PubMed] [Google Scholar]
  14. Saarnio J., Parkkila S., Parkkila A. K., Haukipuro K., Pastoreková S., Pastorek J., Kairaluoma M. I., Karttunen T. J. Immunohistochemical study of colorectal tumors for expression of a novel transmembrane carbonic anhydrase, MN/CA IX, with potential value as a marker of cell proliferation. Am J Pathol. 1998 Jul;153(1):279–285. doi: 10.1016/S0002-9440(10)65569-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Sokoloff M. H., Tso C. L., Kaboo R., Nelson S., Ko J., Dorey F., Figlin R. A., Pang S., deKernion J., Belldegrun A. Quantitative polymerase chain reaction does not improve preoperative prostate cancer staging: a clinicopathological molecular analysis of 121 patients. J Urol. 1996 Nov;156(5):1560–1566. [PubMed] [Google Scholar]
  16. Steffens M. G., Boerman O. C., Oosterwijk-Wakka J. C., Oosterhof G. O., Witjes J. A., Koenders E. B., Oyen W. J., Buijs W. C., Debruyne F. M., Corstens F. H. Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250. J Clin Oncol. 1997 Apr;15(4):1529–1537. doi: 10.1200/JCO.1997.15.4.1529. [DOI] [PubMed] [Google Scholar]
  17. Turner J. R., Odze R. D., Crum C. P., Resnick M. B. MN antigen expression in normal, preneoplastic, and neoplastic esophagus: a clinicopathological study of a new cancer-associated biomarker. Hum Pathol. 1997 Jun;28(6):740–744. doi: 10.1016/s0046-8177(97)90185-4. [DOI] [PubMed] [Google Scholar]
  18. Uemura H., Beniers A. J., Okajima E., Debruyne F. M., Oosterwijk E. Vaccination with anti-idiotype antibodies mimicking a renal cell carcinoma-associated antigen induces tumor immunity. Int J Cancer. 1994 Aug 15;58(4):555–561. doi: 10.1002/ijc.2910580418. [DOI] [PubMed] [Google Scholar]
  19. Uemura H., Okajima E., Debruyne F. M., Oosterwijk E. Internal image anti-idiotype antibodies related to renal-cell carcinoma-associated antigen G250. Int J Cancer. 1994 Feb 15;56(4):609–614. doi: 10.1002/ijc.2910560424. [DOI] [PubMed] [Google Scholar]
  20. Wirth M. P. Immunotherapy for metastatic renal cell carcinoma. Urol Clin North Am. 1993 May;20(2):283–295. [PubMed] [Google Scholar]
  21. van Dijk J., Uemura H., Beniers A. J., Peelen W. P., Zegveld S. T., Fleuren G. J., Warnaar S. O., Oosterwijk E. Therapeutic effects of monoclonal antibody G250, interferons and tumor necrosis factor, in mice with renal-cell carcinoma xenografts. Int J Cancer. 1994 Jan 15;56(2):262–268. doi: 10.1002/ijc.2910560220. [DOI] [PubMed] [Google Scholar]

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