Skip to main content
NCBI home page
Transactions of the American Clinical and Climatological Association logoLink to Transactions of the American Clinical and Climatological Association
. 1989;100:31–38.

Anti-EGF receptor monoclonal antibodies: biological studies and potential clinical applications.

J Mendelsohn 1
PMCID: PMC2376448  PMID: 3077575

Abstract

We have produced two monoclonal antibodies (mAbs), 528 IgG2a and 225 IgG1, which bind to the human EGF receptor with an affinity comparable to EGF, compete with EGF for binding to the receptor, and prevent EGF-induced activation of receptor tyrosine kinase. The mAbs inhibit the proliferation of a number of human tumor cells bearing high numbers of EGF receptors in culture and in nude mouse xenographs. A431 xenographs bearing high numbers of EGF receptors can be imaged with 111In-labeled mAb. Phase I trials were initiated in patients with advanced squamous cell carcinoma of the lung, which consistently expresses high numbers of EGF receptors. 111In-labeled 225 IgG1 was given by single intravenous infusion. Preliminary results show no toxicity from doses up to 120 mg. Tumor visualization was seen to be dose-related. However, as with other imaging studies with indium-labeled antibodies, significant liver and bowel isotope uptake was observed. Further dose escalation is ongoing to assess the relationship between dose and tumor uptake.

Full text

PDF
31

Images in this article

33Fig. 2
on p.33

Selected References

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

  1. Barnes D. W. Epidermal growth factor inhibits growth of A431 human epidermoid carcinoma in serum-free cell culture. J Cell Biol. 1982 Apr;93(1):1–4. doi: 10.1083/jcb.93.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cowley G. P., Smith J. A., Gusterson B. A. Increased EGF receptors on human squamous carcinoma cell lines. Br J Cancer. 1986 Feb;53(2):223–229. doi: 10.1038/bjc.1986.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Derynck R., Goeddel D. V., Ullrich A., Gutterman J. U., Williams R. D., Bringman T. S., Berger W. H. Synthesis of messenger RNAs for transforming growth factors alpha and beta and the epidermal growth factor receptor by human tumors. Cancer Res. 1987 Feb 1;47(3):707–712. [PubMed] [Google Scholar]
  4. Derynck R., Roberts A. B., Winkler M. E., Chen E. Y., Goeddel D. V. Human transforming growth factor-alpha: precursor structure and expression in E. coli. Cell. 1984 Aug;38(1):287–297. doi: 10.1016/0092-8674(84)90550-6. [DOI] [PubMed] [Google Scholar]
  5. Fabricant R. N., De Larco J. E., Todaro G. J. Nerve growth factor receptors on human melanoma cells in culture. Proc Natl Acad Sci U S A. 1977 Feb;74(2):565–569. doi: 10.1073/pnas.74.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Filmus J., Pollak M. N., Cailleau R., Buick R. N. MDA-468, a human breast cancer cell line with a high number of epidermal growth factor (EGF) receptors, has an amplified EGF receptor gene and is growth inhibited by EGF. Biochem Biophys Res Commun. 1985 Apr 30;128(2):898–905. doi: 10.1016/0006-291x(85)90131-7. [DOI] [PubMed] [Google Scholar]
  7. Gill G. N., Kawamoto T., Cochet C., Le A., Sato J. D., Masui H., McLeod C., Mendelsohn J. Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. J Biol Chem. 1984 Jun 25;259(12):7755–7760. [PubMed] [Google Scholar]
  8. Gill G. N., Lazar C. S. Increased phosphotyrosine content and inhibition of proliferation in EGF-treated A431 cells. Nature. 1981 Sep 24;293(5830):305–307. doi: 10.1038/293305a0. [DOI] [PubMed] [Google Scholar]
  9. Gullick W. J., Marsden J. J., Whittle N., Ward B., Bobrow L., Waterfield M. D. Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res. 1986 Jan;46(1):285–292. [PubMed] [Google Scholar]
  10. Hendler F. J., Ozanne B. W. Human squamous cell lung cancers express increased epidermal growth factor receptors. J Clin Invest. 1984 Aug;74(2):647–651. doi: 10.1172/JCI111463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hwang D. L., Tay Y. C., Lin S. S., Lev-Ran A. Expression of epidermal growth factor receptors in human lung tumors. Cancer. 1986 Nov 15;58(10):2260–2263. doi: 10.1002/1097-0142(19861115)58:10<2260::aid-cncr2820581017>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  12. Kawamoto T., Mendelsohn J., Le A., Sato G. H., Lazar C. S., Gill G. N. Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells. J Biol Chem. 1984 Jun 25;259(12):7761–7766. [PubMed] [Google Scholar]
  13. Kawamoto T., Sato J. D., Le A., Polikoff J., Sato G. H., Mendelsohn J. Growth stimulation of A431 cells by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1337–1341. doi: 10.1073/pnas.80.5.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Libermann T. A., Razon N., Bartal A. D., Yarden Y., Schlessinger J., Soreq H. Expression of epidermal growth factor receptors in human brain tumors. Cancer Res. 1984 Feb;44(2):753–760. [PubMed] [Google Scholar]
  15. Masui H., Kawamoto T., Sato J. D., Wolf B., Sato G., Mendelsohn J. Growth inhibition of human tumor cells in athymic mice by anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res. 1984 Mar;44(3):1002–1007. [PubMed] [Google Scholar]
  16. Masui H., Moroyama T., Mendelsohn J. Mechanism of antitumor activity in mice for anti-epidermal growth factor receptor monoclonal antibodies with different isotypes. Cancer Res. 1986 Nov;46(11):5592–5598. [PubMed] [Google Scholar]
  17. Mendelsohn J., Masui H., Goldenberg A. Anti-epidermal growth factor receptor monoclonal antibodies may inhibit A431 tumor cell proliferation by blocking an autocrine pathway. Trans Assoc Am Physicians. 1987;100:173–178. [PubMed] [Google Scholar]
  18. Ozanne B., Richards C. S., Hendler F., Burns D., Gusterson B. Over-expression of the EGF receptor is a hallmark of squamous cell carcinomas. J Pathol. 1986 May;149(1):9–14. doi: 10.1002/path.1711490104. [DOI] [PubMed] [Google Scholar]
  19. Sato J. D., Kawamoto T., Le A. D., Mendelsohn J., Polikoff J., Sato G. H. Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors. Mol Biol Med. 1983 Dec;1(5):511–529. [PubMed] [Google Scholar]
  20. Sunada H., Magun B. E., Mendelsohn J., MacLeod C. L. Monoclonal antibody against epidermal growth factor receptor is internalized without stimulating receptor phosphorylation. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3825–3829. doi: 10.1073/pnas.83.11.3825. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Transactions of the American Clinical and Climatological Association are provided here courtesy of American Clinical and Climatological Association

RESOURCES