Skip to main content
SpringerLink
Log in

Biological studies and potential therapeutic applications of monoclonal antibodies and small molecules reactive with theneu/c-erbB-2 protein

  • Published:
Cell Biophysics Aims and scope Submit manuscript

Abstract

The overexpression of the growth factor receptor p185neu/c-erbB-2 has been observed in a number of human adenocarcinomas and is mechanistically linked to neoplastic growth. Monoclonal antibodies raised against extracellular domains of the p185neu/c-erbB-2 receptor oncoprotein have been utilized to inhibit the pathway ofneu-induced tumor development. Our laboratory has demonstrated a direct effect of anti-p185neu/c-erbB2 antibodies which requires receptor ligation. This induced aggregation causes the downmodulation of cell-surface expression and eventual degradation of p185neu/c-erbB-2 protein. In cells transformed by theneu oncogene, the result of antibody-induced p185neu/c-erbB-2 receptor modulation is the reversion of the malignant pheno-type. We are exploiting the direct efficacy of this monoclonal antibody by developing small molecules (peptides and organic mimietics) based on anti-p185neu/c-erbB-2 antibody structure that can mediate similar receptor binding and biological effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Myers, J. N., Kokai, Y., Cohen, J. A., and Greene, M. I. (1988)The Year in Immunology, vol. 5 (Cruse, J. M. and Lewis, R. E., eds.), Karger, Basel, pp. 178–194.

    Google Scholar 

  2. Waldmann, T. A. (1991)Science 252, 1657.

    Article  PubMed  CAS  Google Scholar 

  3. Carrol, A. M. and Greene, M. I. (1988),Antibodies in Radiodiagnosis and Therapy. (Zabutsky, M. R. ed.), CRC Press, Boca Raton, FL, pp. 13–43.

    Google Scholar 

  4. Urban, J. L. and Schreiber, H. (1992)Annu. Rev. Immunol. 10, 617.

    Article  PubMed  CAS  Google Scholar 

  5. Morrison, S. L. (1992)Annu. Rev. Immunol. 10, 239.

    PubMed  CAS  Google Scholar 

  6. Schecter, A. L., Stern, D. F., Vaidyanathan, L., Decker, S. J., Drebin, J. A., Greene, M. I., et al. (1984)Nature 312, 513.

    Article  Google Scholar 

  7. Drebin, J. A., Stern, D. F., Link, V. C., Weinberg, R. A., and Greene, M. I. (1984)Nature 312, 545.

    Article  PubMed  CAS  Google Scholar 

  8. Weiner, D. B., Liu, J., Cohen, J. A., Williams, W. V., and Greene, M. I. (1989)Nature 339, 230.

    Article  PubMed  CAS  Google Scholar 

  9. Ullrich, A. and Schlessinger, J. (1990)Cell 61, 203.

    Article  PubMed  CAS  Google Scholar 

  10. Dobashi, K., Davis, J., Mikami, Y., Freeman, J. K., Hamuro, J., and Greene, M. I. (1991)Proc. Natl. Acad. Sci. USA 88, 8582.

    Article  PubMed  CAS  Google Scholar 

  11. Lupu, R., Colomer, R., Kannan, B., and Lippman, M. E. (1992)Proc. Natl. Acad. Sci. USA 89, 2287.

    Article  PubMed  CAS  Google Scholar 

  12. Holmes, W. E., Sliwkowski, M. X., Akita, R., Henzel, W., Lee, J., Park, J., et al. (1992)Science 256, 1205.

    Article  PubMed  CAS  Google Scholar 

  13. Huang, S. S. and Huang, J. S. (1992)J. Biol. Chem. 267, 11508.

    PubMed  CAS  Google Scholar 

  14. Peles, E., Bacus, S., Koski, R., Lu, H., Wen, D., Ogden, S., et al. (1992)Cell 69, 205.

    Article  PubMed  CAS  Google Scholar 

  15. Falls, D. L., Rosen, K. M., Corfas, G., Lane, W., and Fischbach, G. (1993)Cell 72, 801.

    Article  PubMed  CAS  Google Scholar 

  16. Coussens, L., Yang-Feng, T. L., Liao, Y., Chen, E., Gray, A., McGrath, J., et al. (1985)Science 230, 1132.

    Article  PubMed  CAS  Google Scholar 

  17. Akiyama, T., Sudo, C., Ogawara, H., Toyoshima, K., and Yamamoto, T. (1986)Science 232, 1644.

    Article  PubMed  CAS  Google Scholar 

  18. Slamon, D. J., Godolphin, W., Jones, L. A., Holt, J., Wong, S. G., Udove, J., et al. (1989)Science 244, 707.

    Article  PubMed  CAS  Google Scholar 

  19. Maguire, H. C. and Greene, M. I. (1990)Pathobiology 58, 297.

    PubMed  Google Scholar 

  20. Gullick, W. J. (1990)Int. J. Cancer 5, 55.

    Article  CAS  Google Scholar 

  21. Kern, J. A., Schwartz, D., Nordberg, J. A., Weiner, D. B., Greene, M. I., Torney, L., et al. (1990)Cancer Res. 50, 5184.

    PubMed  CAS  Google Scholar 

  22. Cohen, J. A., Weiner, D. B., More, K. F., Kokai, Y., Williams, W. V., Maguire, H. C., et al. (1989)Oncogene 4, 81.

    PubMed  CAS  Google Scholar 

  23. Williams, T., Weiner, D. B., Greene, M. I., and Maguire, H. C. (1991)Pathobiology 59, 46.

    PubMed  CAS  Google Scholar 

  24. DiFiore, P. P., Segatto, O., and Aaronson, S. A. (1991)Meth. Enzymol. 198, 272.

    CAS  Google Scholar 

  25. Myers, J. N., Drebin, J. A., Wada, T., and Greene, M. I. (1991)Meth. Enzymol. 198, 277.

    Article  PubMed  CAS  Google Scholar 

  26. Drebin, J. A., Link, V. C., and Greene, M. I. (1988)Oncogene 2, 273.

    PubMed  CAS  Google Scholar 

  27. LeVea, C. M., Myers, J. N., Dougall, W. C., Qian, X., and Greene, M. I. (1993)Receptor, in press.

  28. Drebin, J. A., Link, V. C., Stern, D. F., Weinberg, R. A., and Greene, M. I. (1985)Cell 41, 695.

    Article  Google Scholar 

  29. Shepard, H. M., Lewis, G. D., Sarup, J. C., Fendly, B. M., Maneval, D., Mordenti, J., et al. (1991)J. Clin. Immunol. 11, 117.

    Article  PubMed  CAS  Google Scholar 

  30. Drebin, J. A., Link, V. C., Weinberg, R. A., and Greene, M. I. (1986)Proc. Natl. Acad. Sci. USA 89, 2287.

    Google Scholar 

  31. Drebin, J. A., Link, V. C., and Greene, M. I. (1988)Oncogene 2, 387.

    PubMed  CAS  Google Scholar 

  32. Kumar, R., Shepard, H. M., and Mendelsohn, J. (1991)Mol. Cell. Biol. 11, 979.

    PubMed  CAS  Google Scholar 

  33. Stancovski, I., Hurwitz, E., Leitner, O., Ullrich, A., Yarden, Y., and Sela, M. (1991)Proc. Natl. Acad. Sci. USA 88, 8691.

    Article  PubMed  CAS  Google Scholar 

  34. De Santes, K., Slamon, D., Anderson, S., Shepard, M., Fendly, B., Maneval, D., et al. (1992)Cancer Res. 52, 1916.

    PubMed  Google Scholar 

  35. Harwerth, I. M., Wels, W., Marte, B. M., and Hynes, N. E. (1992)J. Biol. Chem. 267, 15160.

    PubMed  CAS  Google Scholar 

  36. Brandt, Rauf, P. W., Rackovsky, S., and Pincus, M. R. (1990)Proc. Natl. Acad. Sci. USA 87, 8660.

    Article  Google Scholar 

  37. Wada, T., Myers, J. N., Kokai, Y., Brown, V. I., Hamuro, J., LeVea, C. M., et al. (1990)Oncogene 5, 489.

    PubMed  CAS  Google Scholar 

  38. Riechmann, L., Clark, M., Waldmann, H., and Winter, G. (1988)Nature 332, 323.

    Article  PubMed  CAS  Google Scholar 

  39. Winter, G. and Milstein, C. (1991)Nature 349, 293.

    Article  PubMed  CAS  Google Scholar 

  40. Pluckthun, A. (1991)Methods 2, 88.

    Article  Google Scholar 

  41. Saragovi, H. U., Greene, M. I., Chrusciel, R. A., and Kahn, M. (1992)Bio/Technology 10, 773.

    Article  PubMed  CAS  Google Scholar 

  42. Chothia, C. and Lesk, A. M. (1987)J. Mol. Biol. 196, 901.

    Article  PubMed  CAS  Google Scholar 

  43. Williams, W. V., Kieber-Emmons, T., VonFeldt, J., Greene, M. I., and Weiner, D. B. (1991)J. Biol. Chem. 266, 5182.

    PubMed  CAS  Google Scholar 

  44. Saragovi, H. U., Fitzpatrick, D., Raktabutr, A., Nakanishi, H., Kahn, M., and Greene, M. I. (1991)Science 253, 792.

    Article  PubMed  CAS  Google Scholar 

  45. Wada, T., Qian, X., and Greene, M. I. (1990)Cell 61, 1339.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Receptor Biology, Division of Immunology, Room 252 John Morgan Building, 36th and Hamilton Walk, Department of Pathology and Laboratory, Medicine, University of Pennsylvania School of Medicine, 19104, Philadelphia, PA

    William C. Dougall & Mark I. Greene

Authors
  1. William C. Dougall
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark I. Greene
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dougall, W.C., Greene, M.I. Biological studies and potential therapeutic applications of monoclonal antibodies and small molecules reactive with theneu/c-erbB-2 protein. Cell Biophysics 24, 209–218 (1994). https://doi.org/10.1007/BF02789231

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02789231

Index Entries

Search

Navigation