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Modulation of Growth Factor Receptor Expression by Irradiation for Immunotoxin Targeting

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Immunotoxin Methods and Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 166))

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Abstract

Immunotoxins, characterized by tumor-specific cytotoxicity and high potency, have been developed as one of the new promising treatment modalities for primary malignant brain tumors (1–3). Fusion toxins bind to the cell-surface receptor specific for them, are internalized by receptor-mediated endocytosis, and inhibit protein synthesis, causing apoptotic cell death (4, 5 . The cytotoxic activity of the immunotoxin can be influenced by many factors, such as binding to the receptor, intracellular routing, degradation in the lysosome by enzymes, and immunogenicity (3. The first step in the mechanism of action of the immunotoxin is binding to its receptor.

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References

  1. Hall, W.A. and Fodstad, O. (1992) Immunotoxins and central nervous system neoplasia. J. Neurosurg. 76, 1–12.

    Article  PubMed  CAS  Google Scholar 

  2. Hall, W.A. (1997) Targeted toxin therapy, in Advances in Neuro-Oncology II (Kornblith, P. L. and Walker, M. D., eds.), Futura Publishing Co., Armonk, NY, pp. 505–516.

    Google Scholar 

  3. Youle, R.J. (1996) Immunotoxins for central nervous system malignancy. Semin. Cancer Biol. 7, 65–70.

    Article  PubMed  CAS  Google Scholar 

  4. Pastan, I., Willingham, M.C., and FitzGerald, D. J. P. (1986) Immunotoxins. Cell 47, 641–648.

    Article  PubMed  CAS  Google Scholar 

  5. Youle, R.J. and Neville, D. M. Jr. (1987) Role of endocytosis and receptor recycling in ligand-toxin and antibody-toxin conjugate activity, in Immunoconjugates: Antibody Conjugates in Radioimaging and Therapy of Cancer (Vogel, C. W., ed.), Oxford University Press, New York, NY, pp. 153–169.

    Google Scholar 

  6. Yarden, Y. and Ullrich, A. (1988) Growth factor receptor tyrosine kinases. Annu. Rev. Biochem. 57, 443–478.

    Article  PubMed  CAS  Google Scholar 

  7. Ullrich, A. and Schlessinger, J. (1990) Signal transduction by receptors with tyrosine kinase activity. Cell 61, 203–212.

    Article  PubMed  CAS  Google Scholar 

  8. Goumnerova, L.C. and Guha, A. (1993) Oncogenes and growth factors in human astrocytomas, in Astrocytomas: Diagnosis, Treatment, and Biology (Black, P.M., Schoene, W.C., and Lampson, L. A., eds.), Blackwell Scientific Publications, Cambridge, MA, pp. 211–227.

    Google Scholar 

  9. van der Geer, P., Hunter, T., and Lindberg, R. A. (1994) Receptor proteintyrosine kinases and their signal transduction pathways. Annu. Rev. Cell Biol. 10, 251–337.

    Article  PubMed  Google Scholar 

  10. Lala, P., Angelov, L., Provias, J., and Guha, A. (1997) Growth factors and nervous system tumors, in Cancer of the Nervous System (Black, P. M. and Loeffler, J. S., eds.), Blackwell Science, Cambridge, MA, pp. 744–772.

    Google Scholar 

  11. Heldin, C. H., Wasteson, A., and Westermark, B. (1982) Interaction of plateletderived growth factor with its fibroblast receptor. J. Biol. Chem. 257, 4216–4221.

    PubMed  CAS  Google Scholar 

  12. Beguinot, L., Lyall, R. M., Willingham, M. C., and Pastan, I. (1984) Down-regulation of the epidermal growth factor receptor in KB cells is due to receptor internalization and subsequent degradation in lysosomes. Proc. Natl. Acad. Sci. USA 81, 2384–2388.

    Article  PubMed  CAS  Google Scholar 

  13. Stoscheck, C. M. and Carpenter, G. (1984) Down regulation of epidermal growth factor receptors: direct demonstration of receptor degradation in human fibroblasts. J. Cell Biol. 98, 1048–1053.

    Article  PubMed  CAS  Google Scholar 

  14. Subtil, A., Hemar, A., and Dautry-Varsat, A. (1994) Rapid endocytosis of interleukin 2 receptors when clathrin-coated pit endocytosis is inhibited. J. Cell Sci. 107, 3461–3468.

    PubMed  CAS  Google Scholar 

  15. Hemar, A., Subtil, A., Lieb, M., Morelon, E., Hellio, R., and Dautry-Varsat, A. (1995) Endocytosis of interleukin 2 receptors in human T lymphocytes: distinct intracellular localization and fate of the receptor α, β, and γ chains. J. Cell Biol. 129, 55–64.

    Article  PubMed  CAS  Google Scholar 

  16. Glenney, J. R. Jr., Chen, W. S., Lazar, C. S., Walton, G. M., Zokas, L. M., Rosenfeld, M. G., et al. (1988) Ligand-induced endocytosis of the EGF receptor is blocked by mutational inactivation and by microinjection of anti-phosphotyrosine antibodies. Cell 52, 675–684.

    Article  PubMed  CAS  Google Scholar 

  17. Sorkin, A., Westermark, B., Heldin, C. H., and Claesson-Welsh, L. (1991) Effect of receptor kinase inactivation on the rate of internalization and degradation of PDGF and the PDGF β-receptor. J. Cell Biol. 112, 469–478.

    Article  PubMed  CAS  Google Scholar 

  18. Felder, S., LaVin, J., Ullrich, A., and Schlessinger, J. (1992) Kinetics of binding, endocytosis, and recycling of EGF receptor mutants. J. Cell Biol. 117, 203–212.

    Article  PubMed  CAS  Google Scholar 

  19. Sorkin, A., Helin, K., Waters, C. M., Carpenter, G., and Beguinot, L. (1992) Multiple autophosphorylation sites of the epidermal growth factor receptor are essential for receptor kinase activity and internalization. J. Biol. Chem. 267, 8672–8678.

    PubMed  CAS  Google Scholar 

  20. Schneider, C., Sutherland, R., Newman, R., and Greaves, M. (1982) Structural features of the cell surface receptor for transferrin that is recognized by the monoclonal antibody OKT9. J. Biol. Chem. 257, 8516–8522.

    PubMed  CAS  Google Scholar 

  21. Joly, M., Kazlauskas, A., Fay, F. S., and Corvera, S. (1994) Disruption of PDGF receptor trafficking by mutation of its PI-3 kinase binding sites. Science 263, 684–687.

    Article  PubMed  CAS  Google Scholar 

  22. Sorkin, A. (1996) Receptor-mediated endocytosis of growth factors, in Signal Transduction (Heldin, C. H. and Purton, M., eds.), Chapman & Hall, London, pp. 109–123.

    Google Scholar 

  23. Johnson, V. G., Wrobel, C., Wilson, D., Zovickian, J., Greenfield, L., Oldfield, E. H., et al. (1989) Improved tumor-specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia. J. Neurosurg. 70, 240–248.

    Article  PubMed  CAS  Google Scholar 

  24. Laske, D. W., Youle, R. J., and Oldfield, E. H. (1997) Tumor regression with regional distribution of the targeted toxin TF-CRM 107 in patients with malignant brain tumors. Nature Med. 3, 1362–1368. Irradiation-Induced Receptor Modulation 109

    Article  PubMed  CAS  Google Scholar 

  25. Husain, S. R., Behari, N., Kreitman, R. J., Pastan, I., and Puri, R. K. (1998) Complete regression of established human glioblastoma tumor xenograft by interleukin-4 toxin therapy. Cancer Res. 58, 3649–3653.

    PubMed  CAS  Google Scholar 

  26. Puri, R. K., Hoon, D. S., Leland, P., Snoy, P., Rand, R. W., Pastan, I., et al. (1996) Preclinical development of a recombinant toxin containing circularly permuted interleukin 4 and truncated Pseudomonas exotoxin for therapy of malignant astrocytoma. Cancer Res. 56, 5631–5637.

    PubMed  CAS  Google Scholar 

  27. Trowbridge, I. S., Newman, R. A., Domingo, D. L., and Sauvage, C. (1984) Transferrin receptors: structure and function. Biochem. Pharmacol. 33, 925–932.

    Article  PubMed  CAS  Google Scholar 

  28. Trowbridge, I. S. and Shackelford, D. A. (1986) Structure and function of transferrin receptors and their relationship to cell growth. Biochem. Soc. Symp. 51, 117–129.

    PubMed  CAS  Google Scholar 

  29. Ohara, J. and Paul, W. E. (1987) Receptors for B-cell stimulatory factor-1 expressed on cells of haematopoietic lineage. Nature 325, 537–540.

    Article  PubMed  CAS  Google Scholar 

  30. Park, L. S., Friend, D., Sassenfeld, H. M., and Urdal, D. L. (1987) Characterization of the human B cell stimulatory factor 1 receptor. J. Exp. Med. 166, 476–488.

    Article  PubMed  CAS  Google Scholar 

  31. Park, L. S., Friend, D., Grabstein, K., and Urdal, D. L. (1987) Characterization of the high-affinity cell-surface receptor for murine B-cell-stimulating factor 1. Proc. Natl. Acad. Sci. USA 84, 1669–1673.

    Article  PubMed  CAS  Google Scholar 

  32. Lowenthal, J. W., Castle, B. E., Christiansen, J., Schreurs, J., Rennick, D., Arai, N., et al. (1988) Expression of high affinity receptors for murine interleukin 4 (BSF-1) on hemopoietic and nonhemopoietic cells. J. Immunol. 140, 456–464.

    PubMed  CAS  Google Scholar 

  33. Paul, W. E. (1991) Interleukin-4: A prototypic immunoregulatory lymphokine. Blood 77, 1859–1870.

    PubMed  CAS  Google Scholar 

  34. Gammeltoft, S., Haselbacher, G. K., Humbel, R. E., Fehlmann, M., and Van Obberghen, E. (1985) Two types of receptor for insulin-like growth factors in mammalian brain. EMBOJ 4, 3407–3412.

    CAS  Google Scholar 

  35. Gammeltoft, S., Ballotti, R., Kowalski, A., Westermark, B., and Van Obberghen, E. (1988) Expression of two types of receptor for insulin-like growth factors in human malignant glioma. Cancer Res. 48, 1233–1237.

    PubMed  CAS  Google Scholar 

  36. Glick, R. P., Lichtor, T., and Unterman, T. G. (1997) Insulin-like growth factors in central nervous system tumors. J. Neurooncol. 35, 315–325.

    Article  PubMed  CAS  Google Scholar 

  37. Ullrich, A., Gray, A., Tam, A. W., Yang-Feng, T., Tsubokawa, M., Collins, C., et al. (1986) Insulin-like growth factor 1 receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBOJ 5, 2503–2512.

    CAS  Google Scholar 

  38. Ballotti, R., Nielsen, F. C., Pringle, N., Kowalski, A., Richardson, W. D., Van Obberghen, E., et al. (1987) Insulin-like growth factor 1 in cultured rat astrocytes: expression of the gene, and receptor tyrosine kinase. EMBOJ 6, 3633–3639.

    CAS  Google Scholar 

  39. Jacobs, S., Kull, F. C. Jr., Earp, H. S., Svoboda, M. E., Van Wyk, J. J., and Cuatrecasas, P. (1983) Somatomedin-C stimulates the phosphorylation of the betasubunit of its own receptor. J. Biol. Chem. 258, 9581–9584.

    PubMed  CAS  Google Scholar 

  40. Rubin, J. B., Shia, M. A., and Pilch, P. F. (1983) Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor I. Nature 305, 438–440.

    Article  PubMed  CAS  Google Scholar 

  41. Zick, Y., Sasaki, N., Rees-Jones, R. W., Grunberger, G., Nissley, S. P., and Rechler, M. M. (1984) Insulin-like growth factor-I (IGF-I) stimulates tyrosine kinase activity in purified receptors from a rat liver cell line. Biochem. Biophys. Res. Commun. 119, 6–13.

    Article  PubMed  CAS  Google Scholar 

  42. Hall, E. J. (1994) Radiobiology for the Radiologist. J. B. Lippincott Co., Philadelphia, PA.

    Google Scholar 

  43. Kolker, J. D. and Weichselbaum, R. R. (1997) Radiobiology update, in Advances in Neuro-Oncology II (Kornblith, P. L. and Walker, M. D., eds.), Futura Publishing Co., Armonk, NY, pp. 283–305.

    Google Scholar 

  44. Matsuo, T., Ohtsuru, A., Ito, M., Komatsu, K., Okumura, Y., Numba, H., et al. (1995) Inhibition of epidermal growth factor binding system by ionizing radiation in A431 human squamous carcinoma cells. Cancer Lett. 89, 153–159.

    Article  PubMed  CAS  Google Scholar 

  45. Dulic, V., Kaufmann, W. K., Wilson, S. J., Tlsty, T. D., Lees, E., Harper, J. W., et al. (1994) p53-Dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76, 1013–1023.

    Article  PubMed  CAS  Google Scholar 

  46. Chae, H. P., Jarvis, L. J., and Uckun, F. M. (1993) Role of tyrosine phosphorylation in radiation-induced activation of c-jun protooncogene in human lymphohematopoietic precursor cells. Cancer Res. 53, 447–451.

    PubMed  CAS  Google Scholar 

  47. Fuks, Z., Haimovitz-Friedman, A., Hallahan, D. E., Kufe, D. W., and Weichselbaum, R. R. (1993) Stress response genes induced in mammalian cells by ionizing radiation. Radiat. Oncol. Invest. 1, 81–93.

    Article  CAS  Google Scholar 

  48. Uckun, F. M., Schieven, G. L., Tuel-Ahlgren, L. M., Dibirdik, I., Myers, D. E., Ledbetter, J. A., et al. (1993) Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors. Proc. Natl. Acad. Sci. USA 90, 252–256.

    Article  PubMed  CAS  Google Scholar 

  49. Uckun, F. M., Tuel-Ahlgren, L., Song, C. W., Waddick, K., Myers, D. E., Kirihara, J., et al. (1992) Ionizing radiation stimulates unidentified tyrosine-specific protein kinases in human B-lymphocyte precursors, triggering apoptosis and clonogenic cell death. Proc. Natl. Acad. Sci. USA 89, 9005–9009.

    Article  PubMed  CAS  Google Scholar 

  50. Kharbanda, S., Yuan, Z. M., Rubin, E., Weichselbaum, R., and Kufe, D. (1994) Activation of Src-like p56/p53lyn tyrosine kinase by ionizing radiation. J. Biol. Chem. 269, 20,739–20,743.

    PubMed  CAS  Google Scholar 

  51. Peter, R. U., Beetz, A., Ried, C., Michel, G., vanBeuningen, D., and Ruzicka, T. (1993) Increased expression of the epidermal growth factor receptor in human epidermal keratinocytes after exposure to ionizing radiation. Radiat. Res. 136, 65–70.

    Article  PubMed  CAS  Google Scholar 

  52. Schmidt-Ullrich, R. K., Valerie, K., Chan, W., Wazer, D. E., and Lin, P. S. (1992) Expression of oestrogen receptor and transforming growth factor in MCF-7 cells after exposure to fractionated irradiation. Int. J. Radiat. Biol. 61, 405–415.

    Article  PubMed  CAS  Google Scholar 

  53. Schmidt-Ullrich, R. K., Valerie, K. C., Chan, W., and McWilliams, D. (1994) Altered expression of epidermal growth factor receptor and estrogen receptor in MCF-7 cells after single and repeated radiation exposures. Int. J. Radiat. Oncol. Biol. Phys. 29, 813–819.

    Article  PubMed  CAS  Google Scholar 

  54. Schmidt-Ullrich, R. K., Valerie, K., Fogleman, P. B., and Walters, J. (1996) Radiation-induced autophosphorylation of epidermal growth factor receptor in human malignant mammary and squamous epithelial cells. Radiat. Res. 145, 81–85.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Neurosurgery, University of Minnesota, Minneapolis, MN

    Ki-Uk Kim, Hsiao-Tzu Ni, Stephen R. Spellman, Walter C. Low & Walter A. Hall

  2. Department of Therapeutic Radiology, University of Minnesota, Minneapolis, MN

    Kwan H. Cho

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  1. Ki-Uk Kim
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  2. Hsiao-Tzu Ni
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  3. Stephen R. Spellman
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  4. Kwan H. Cho
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  5. Walter C. Low
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  6. Walter A. Hall
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Editors and Affiliations

  1. Department of Neurosurgery, University of Minnesota, Minneapolis, Minnesota

    Walter A. Hall MD

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© 2001 Humana Press Inc., Totowa, NJ

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Kim, KU., Ni, HT., Spellman, S.R., Cho, K.H., Low, W.C., Hall, W.A. (2001). Modulation of Growth Factor Receptor Expression by Irradiation for Immunotoxin Targeting. In: Hall, W.A. (eds) Immunotoxin Methods and Protocols. Methods in Molecular Biology™, vol 166. Humana Press. https://doi.org/10.1385/1-59259-114-0:101

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  • DOI: https://doi.org/10.1385/1-59259-114-0:101

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-775-5

  • Online ISBN: 978-1-59259-114-5

  • eBook Packages: Springer Protocols

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