Combination Therapy with Cisplatinum and EGF Receptor Blockade

  • John Mendelsohn
  • Zhen Fan
  • Jose Baselga
Chapter

Abstract

Simultaneous treatment of xenografts of human A431 vulvar squamous carcinoma cells and MDA-468 breast adenoma cells with anti-EGF receptor monoclonal antibody (MAb) plus maximal tolerated doses of cisplatinum (cis-DDP) results in eradication of well-established tumors that are resistant to either therapy when administered alone. Hypotheses that could explain this synergistic antitumor activity are presented. We suggest that activation of dual checkpoints by the combination therapy results in cell death.

Keywords

Epidermal Growth Factor Receptor A431 Cell Receptor Monoclonal Antibody Combination Of225 Synergistic Antitumor Activity 
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References

  1. 1.
    T. Kawamoto, J.D. Sato, A. Le, J. Polikoff, G.H. Sato, and J. Mendelsohn, Growth stimulation of A431 cells by EGF: Identification of high affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody, Proc Natl Acad Sci USA. 80:1337 (1983).CrossRefPubMedGoogle Scholar
  2. 2.
    J.D. Sato, T. Kawamoto, A.D. Le, J. Mendelsohn, J. Polikoff, and G.H. Sato, Biological effect in vitro of monoclonal antibodies to human EGF receptors, Mol Biol Med 1:511 (1983).PubMedGoogle Scholar
  3. 3.
    G.N. Gill, T. Kawamoto, C. Cochet, A. Le, J.D. Sato, H. Masui, C.L. MacLeod, and J. Mendelsohn, Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity, J Biol Chem 259:7755 (1984).PubMedGoogle Scholar
  4. 4.
    S.D. Markowitz, K. Molkentin, C. Gerbic, J. Jackson, T. Stellato, and J.K.V. Willson, Growth stimulation by coexpression of transforming growth factor a and epidermal growth factor-receptor in normal and adenomatous human colon epithelium, J Clin Invest 86:356 (1990).CrossRefPubMedGoogle Scholar
  5. 5.
    S.E. Bates, E.M. Valverius, B.W. Ennis, D.A. Bronzert, J.P. Sheridan, M.R. Stampfer, J. Mendelsohn J, Lippman ME, Dickson RB. Expression of the TGF±/EGF Receptor Pathway in normal human breast epithelial cells, Endocrinol 126:596 (1990).CrossRefGoogle Scholar
  6. 6.
    M.R. Stampfer, C.H. Pan, J. Hosoda, J. Bartholomew, J. Mendelsohn, and P. Yaswen, Blockage of EGF receptor signal transduction causes reversible arrest of normal and immortal human mammary epithelial cells with synchronous reentry into the cell cycle, Exp Cell Res 208:175 (1993).CrossRefPubMedGoogle Scholar
  7. 7.
    M. Van de Vijver, R. Kumar, and J. Mendelsohn, Ligand-induced activation of A431 cell EGF receptors occurs primarily by an autocrine pathway that acts upon receptors on the surface rather than intracellularly, J Biol Chem 266:7503 (1991).PubMedGoogle Scholar
  8. 8.
    T. Kawamoto, J. Mendelsohn, A. Le, G.H. Sato, C.S. Lazar, and G.N. Gill, Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells. J Biol Chem 259:7761 (1984).PubMedGoogle Scholar
  9. 9.
    Z. Fan, H. Masui, I. Atlas, and J. Mendelsohn, Blockade of epidermal growth factor (EGF) receptor function by bivalent and monovalent fragments of 225 anti-EGF receptor monoclonal antibody, Cancer Res 53:4322 (1993).PubMedGoogle Scholar
  10. 10.
    Z. Fan, J. Mendelsohn, H. Masui, and R. Kumar, Regulation of epidermal growth factor receptor in NIH3T3/HER14 cells by antireceptor monoclonal antibodies, J Biol Chem 268:21073 (1993).PubMedGoogle Scholar
  11. U.Z. Fan, Y. Lu, X. Wu, J. Mendelsohn, Antibody-induced epidermal growth factor receptor dimerization mediates inhibition of autocrine proliferation of A431 squamous carcinoma cells, J Biol Chem 269:27595 (1994).PubMedGoogle Scholar
  12. 12.
    M. Reiss, E.B. Stash, V.F. Vellucci, and Z-I. Zhou, Activation of the autocrine transforming growth factor alpha pathway in human squamous carcinoma cells, Cancer Res 51:6254 (1992).Google Scholar
  13. 13.
    W.E.J. Karnes, J.H. Walsh, S.V. Wu, R.S. Kim, M. G. Martin, H.C. Wong, J. Mendelsohn, A.V. Gazdar, and F. Cuttitta, Autocrine stimulation of EGF receptors by TGF-alpha regulates autonomous proliferation of human colon cancer cells, Gaslro 102:474(1992).Google Scholar
  14. 14.
    H. Masui, B. Boman, J. Hyman, L. Castro, and J. Mendelsohn, Treatment with anti-EGF receptor monoclonal antibody causes regression of DiFi human colorectal carcinoma xenografts, Proc of the Amer Assoc for Cancer Res USA, 32:394 (Abs #2340) (1991).Google Scholar
  15. 15.
    D.R. Hofer, E.R. Sherwood, W.D. Bromberg, J. Mendelsohn, C. Lee, and J. M. Kozlowski, Autonomous growth of androgen-independent human prostatic carcinoma cells: Role of transforming growth factor-±. Cancer Res 51:2780 (1991).PubMedGoogle Scholar
  16. 16.
    C-J Fong, E.R. Sherwood, J. Mendelsohn, C. Lee, and J. M. Kozlowski, Epidermal growth factor receptor monoclonal antibody inhibits constitutive receptor phosphorylation, reduces autonomous growth, ans ensitizes androgen-independent prostatic carcinoma cells to tumor necrosis factor-±, Cancer Res 52:5887 (1992).PubMedGoogle Scholar
  17. 17.
    I. Atlas, J. Mendelsohn, J. Baselga, H. Masui, W.R. Fair, and R. Kumar, Growth regulation of human renal carcinoma cells: role of transforming growth factor-±, Cancer Res 52:3335 (1992).PubMedGoogle Scholar
  18. 18.
    M. Lund-Johansen, R. Bjerkvig, P.A. Humphrey, S.H. Bigner, D.D. Bigner, O-D. Laerum, Effect of epidermal growth factor on glioma cell growth, migration, and invasion in vitro, Cancer Res 50:6039 (1990).PubMedGoogle Scholar
  19. 19.
    K-I. Morishige, H. Kurachi, K. Amemiya, Y. Fujita, T. Yamamoto, A. Miyake, and O. Tanizawa, Evidence for the involvement of transforming growth factor alpha and epidermal growth factor receptor autocrine growth mechanism in primary human ovarian cancers in vitro, Cancer Res 51:5322 (1991).PubMedGoogle Scholar
  20. 20.
    K-I. Morishige, H. Kurachi, K. Amemiya, H. Adachi, M. Inoue, A. Miyake, O. Tanizawa, and Y. Sakoyama, Involvement of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vitro. Cancer Res 51:5951 (1991).PubMedGoogle Scholar
  21. 21.
    E. Sturgis, P. Sacks, H. Masui, J. Mendelsohn, and S. Schantz, The effects of anti-epidermal growth factor receptor antibody 528 on the proliferation and differentiation of head and neck cancer. Otolaryngol-Head & Neck Surgery 111:633 (1994).CrossRefGoogle Scholar
  22. 22.
    C.L. Brown, M. Rubin, H. Masui, and J. Mendelsohn, Growth inhibition by anti-EGF receptor monoclonal antibody in squamous cervical carcinoma cells expressing TGF±. Proc Amer Assoc Cancer Res 35:381(Abstr 2270) (1994).Google Scholar
  23. 23.
    C.L. Arteaga, E. Coronado, and C.K. Osborne, Blockade of the epidermal growth factor receptor inhibits transforming growth factor ±-induced but not estrogen-induced growth of hormone-dependent human breast cancer, Mol Endocr 2:1064 (1988).CrossRefGoogle Scholar
  24. 24.
    B.W. Ennis, E.M. Valverius, M.E. Lippman, F. Bellot, R. Kris, J. Schlessinger, H. Masui, A. Goldenberg, J. Mendelsohn, and R. B. Dickson, Monoclonal anti-EGF receptor antibodies inhibit the growth of malignant and non-malignant human mammary epithelial cells, Mol Endocrinol 3:1830(1989).CrossRefPubMedGoogle Scholar
  25. 25.
    H. Masui, T. Kawamoto, J.D. Sato, B. Wolf, G.H. Sato, and J. Mendelsohn, Growth inhibition of human tumor cells in athymic mice by anti-EGF receptor monoclonal antibodies, Cancer Res 44:1002 (1984).PubMedGoogle Scholar
  26. 26.
    J. Mendelsohn, Potential clinical applications of anti-EGF receptor monoclonal antibodies, in: Cancer Cells, M. Furth, and M. Greaves, eds. Cold Spring Harbor Laboratory, New York (1989).Google Scholar
  27. 27.
    I. Atlas, H. Masui, and J. Mendelsohn, In preparation.Google Scholar
  28. 28.
    J. Baselga, L. Norton, H. Masui, A. Pandiella, K. Coplan, C. Cordon-Cardo, W. Miller, and J. Mendelsohn, Anti-tumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies, J Natl Cancer Inst 85:1327(1993).CrossRefPubMedGoogle Scholar
  29. 29.
    Z. Fan, J. Baselga, H. Masui, and J. Mendelsohn, Antitumor effect of anti-EGF receptor monoclonal antibodies plus cis-Diamminedichloroplatinum (cis-DDP) on well established A431 cell xenografts, Cancer Res 53:4637 (1993).PubMedGoogle Scholar
  30. 30.
    E. Aboud-Pirak, E. Hurwitz, M.E. Pirak, F. Bellot, J. Schlessinger, and M. Sela, Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice, J Natl Cancer Inst 80:1605 (1988).CrossRefPubMedGoogle Scholar
  31. 31.
    J. Baselga, L. Norton, K. Coplan, R. Shalaby, and J. Mendelsohn, Antitumor activity of placitaxel in combination with anti-growth factor receptor monoclonal antibodies in breast cancer xenografts, Proc Amer Assoc Cancer Res 35:380(Abstr.2262) (1994).Google Scholar
  32. 32.
    C. Aghajanian, Y. Zhuo, T. Y. Ho, C. Brown, Z. Fan, J. Baselga, J. Mendelsohn, and D.R. Spriggs, Anti-epidermal growth factor receptor monoclonal antibody tratment of A431 cells decreases cisplatin/DNA adduct repair in association with NF-KB induction. Proc Amer. Assoc. for Cancer Res 36(Abst.#2545):427 (1995).Google Scholar
  33. 33.
    R.J. Pietras, B. M. Fendly, V.R. Chazin, M.D. Pegram, S.B. Howell, and D. J. Slamon, Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells, Oncogene 9:1829 (1994).PubMedGoogle Scholar
  34. 34.
    G.I. Evan, A.H. Wyllie, C.S. Gilbert, T.D. Littlewood, H. Land, M. Brooks, C. M. Waters, L. Z. Penn, and D. C. Hancock, Induction of apoptosis in fibroblasts by c-myc protein, Cell 69:119 (1992).CrossRefPubMedGoogle Scholar
  35. 35.
    C.E. Canman, T. M. Gilmer, S. B. Coutts, and M.B. Kastan, Growth factor modulation of p53-mediated growth arrest versus apoptosis, Genes & Develop 9:600 (1995).CrossRefGoogle Scholar
  36. 36.
    G. T. Williams, C.A. Smith, E. Spooncer, T.M. Dexter, and D.R. Taylor, Haemopoietic colony stimulating factors promote cell survival by suppressing opoptosis, Nature 343:76(1990).CrossRefPubMedGoogle Scholar
  37. 37.
    K.W. Kohn, J. Jackman, and P.M. O’Connor, Cell cycle control and cancer chemotherapy, J Cellular Biochem. 54:440 (1994).CrossRefGoogle Scholar
  38. 38.
    L. H. Hartwell, and M.B. Kastan, Cell cycle control and cancer, Science 266:1821 (1994).CrossRefPubMedGoogle Scholar
  39. 39.
    C.R. Divgi, C. Welt, M. Kris, F.X. Real, S.D.J. Yeh, R. Gralla, B. Merchant, S. Schweighart, M. Unger, S. M. Larson, and J. Mendelsohn, Phase I and imaging trial of indium-111 labeled anti-EGF receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma, J Natl Can hist 83:97 (1991).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • John Mendelsohn
    • 1
  • Zhen Fan
    • 1
  • Jose Baselga
    • 1
  1. 1.Memorial Sloan-Kettering Cancer Center and Cornell University Medical CollegeNew YorkUSA

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