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. 1989 Jun;59(6):910–914. doi: 10.1038/bjc.1989.192

Elevated expression of the interleukin 4 receptor in carcinoma: a target for immunotherapy?

B Al Jabaari 1, H M Ladyman 1, M Larché 1, G B Sivolapenko 1, A A Epenetos 1, M A Ritter 1
PMCID: PMC2246718  PMID: 2736228

Abstract

Studies using monoclonal antibody MR6, which is thought to bind to the interleukin-4 growth factor receptor (IL-4R), indicate that IL-4R molecules are upregulated in tumours of epithelial origin and that radiolabelled MR6 is effective as an in vivo tumour imaging agent. Immunohistochemical analysis of a wide range of solid tumours using monoclonal antibody MR6 has demonstrated elevated expression of the IL-4R on a variety of carcinomas. The equivalent normal tissue showed either weak or no expression of this molecule. No other tumours studied were positive. The molecular weight of the receptor on tumour cells was indistinguishable from that on normal tissue. These data raise the possibility that the IL-4R is the product of a novel oncogene such that elevated expression of this growth factor receptor could be involved in the process of carcinogenesis. Monoclonal antibodies to the IL-4R, such as MR6, may therefore be useful reagents not only for diagnosis and immunoscintigraphy, but also for in vivo antibody-guided therapy of epithelial cancers.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adamson E. D. Oncogenes in development. Development. 1987 Apr;99(4):449–471. doi: 10.1242/dev.99.4.449. [DOI] [PubMed] [Google Scholar]
  2. Berger M. S., Gullick W. J., Greenfield C., Evans S., Addis B. J., Waterfield M. D. Epidermal growth factor receptors in lung tumours. J Pathol. 1987 Aug;152(4):297–307. doi: 10.1002/path.1711520408. [DOI] [PubMed] [Google Scholar]
  3. Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
  4. Cerny T., Barnes D. M., Hasleton P., Barber P. V., Healy K., Gullick W., Thatcher N. Expression of epidermal growth factor receptor (EGF-R) in human lung tumours. Br J Cancer. 1986 Aug;54(2):265–269. doi: 10.1038/bjc.1986.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Courtenay-Luck N. S., Epenetos A. A., Winearls C. G., Ritter M. A. Preexisting human anti-murine immunoglobulin reactivity due to polyclonal rheumatoid factors. Cancer Res. 1987 Aug 15;47(16):4520–4525. [PubMed] [Google Scholar]
  6. Epenetos A. A., Courtenay-Luck N., Pickering D., Hooker G., Durbin H., Lavender J. P., McKenzie C. G. Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen. Br Med J (Clin Res Ed) 1985 May 18;290(6480):1463–1466. doi: 10.1136/bmj.290.6480.1463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Farrands P. A., Perkins A. C., Pimm M. V., Embleton M. J., Hardy J. D., Baldwin R. W., Hardcastle J. D. Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody. Lancet. 1982 Aug 21;2(8295):397–400. doi: 10.1016/s0140-6736(82)90437-8. [DOI] [PubMed] [Google Scholar]
  8. Fernandez-Botran R., Krammer P. H., Diamantstein T., Uhr J. W., Vitetta E. S. B cell-stimulatory factor 1 (BSF-1) promotes growth of helper T cell lines. J Exp Med. 1986 Aug 1;164(2):580–593. doi: 10.1084/jem.164.2.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hnatowich D. J., Layne W. W., Childs R. L., Lanteigne D., Davis M. A., Griffin T. W., Doherty P. W. Radioactive labeling of antibody: a simple and efficient method. Science. 1983 May 6;220(4597):613–615. doi: 10.1126/science.6836304. [DOI] [PubMed] [Google Scholar]
  10. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hu-Li J., Shevach E. M., Mizuguchi J., Ohara J., Mosmann T., Paul W. E. B cell stimulatory factor 1 (interleukin 4) is a potent costimulant for normal resting T lymphocytes. J Exp Med. 1987 Jan 1;165(1):157–172. doi: 10.1084/jem.165.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hudziak R. M., Schlessinger J., Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7159–7163. doi: 10.1073/pnas.84.20.7159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  14. Larche M., Lamb J. R., O'Hehir R. E., Imami-Shita N., Zanders E. D., Quint D. E., Moqbel R., Ritter M. A. Functional evidence for a monoclonal antibody that binds to the human IL-4 receptor. Immunology. 1988 Dec;65(4):617–622. [PMC free article] [PubMed] [Google Scholar]
  15. Larché M., Lamb J. R., Ritter M. A. A novel T-lymphocyte molecule that may function in the induction of self-tolerance and MHC-restriction within the human thymic microenvironment. Immunology. 1988 May;64(1):101–105. [PMC free article] [PubMed] [Google Scholar]
  16. Larson S. M., Carrasquillo J. A., Krohn K. A., Brown J. P., McGuffin R. W., Ferens J. M., Graham M. M., Hill L. D., Beaumier P. L., Hellström K. E. Localization of 131I-labeled p97-specific Fab fragments in human melanoma as a basis for radiotherapy. J Clin Invest. 1983 Dec;72(6):2101–2114. doi: 10.1172/JCI111175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lee F., Yokota T., Otsuka T., Meyerson P., Villaret D., Coffman R., Mosmann T., Rennick D., Roehm N., Smith C. Isolation and characterization of a mouse interleukin cDNA clone that expresses B-cell stimulatory factor 1 activities and T-cell- and mast-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2061–2065. doi: 10.1073/pnas.83.7.2061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Merlino G. T., Xu Y. H., Ishii S., Clark A. J., Semba K., Toyoshima K., Yamamoto T., Pastan I. Amplification and enhanced expression of the epidermal growth factor receptor gene in A431 human carcinoma cells. Science. 1984 Apr 27;224(4647):417–419. doi: 10.1126/science.6200934. [DOI] [PubMed] [Google Scholar]
  19. Miller R. A., Oseroff A. R., Stratte P. T., Levy R. Monoclonal antibody therapeutic trials in seven patients with T-cell lymphoma. Blood. 1983 Nov;62(5):988–995. [PubMed] [Google Scholar]
  20. Mosmann T. R., Bond M. W., Coffman R. L., Ohara J., Paul W. E. T-cell and mast cell lines respond to B-cell stimulatory factor 1. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5654–5658. doi: 10.1073/pnas.83.15.5654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Park L. S., Friend D., Sassenfeld H. M., Urdal D. L. Characterization of the human B cell stimulatory factor 1 receptor. J Exp Med. 1987 Aug 1;166(2):476–488. doi: 10.1084/jem.166.2.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Slamon D. J., Clark G. M., Wong S. G., Levin W. J., Ullrich A., McGuire W. L. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987 Jan 9;235(4785):177–182. doi: 10.1126/science.3798106. [DOI] [PubMed] [Google Scholar]
  23. Spitler L. E., del Rio M., Khentigan A., Wedel N. I., Brophy N. A., Miller L. L., Harkonen W. S., Rosendorf L. L., Lee H. M., Mischak R. P. Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. Cancer Res. 1987 Mar 15;47(6):1717–1723. [PubMed] [Google Scholar]
  24. Ullrich A., Coussens L., Hayflick J. S., Dull T. J., Gray A., Tam A. W., Lee J., Yarden Y., Libermann T. A., Schlessinger J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. 1984 May 31-Jun 6Nature. 309(5967):418–425. doi: 10.1038/309418a0. [DOI] [PubMed] [Google Scholar]
  25. Willcox N., Schluep M., Ritter M. A., Schuurman H. J., Newsom-Davis J., Christensson B. Myasthenic and nonmyasthenic thymoma. An expansion of a minor cortical epithelial cell subset? Am J Pathol. 1987 Jun;127(3):447–460. [PMC free article] [PubMed] [Google Scholar]
  26. de Maagd R. A., MacKenzie W. A., Schuurman H. J., Ritter M. A., Price K. M., Broekhuizen R., Kater L. The human thymus microenvironment: heterogeneity detected by monoclonal anti-epithelial cell antibodies. Immunology. 1985 Apr;54(4):745–754. [PMC free article] [PubMed] [Google Scholar]

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