Nuclear Medicine and Biology
Volume 39, Issue 1 , Pages 23-34 , January 2012

Radioimmunotargeting of malignant glioma by monoclonal antibody D2C7 reactive against both wild-type and variant III mutant epidermal growth factor receptors

  • Michael R. Zalutsky

      Affiliations

    • Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 919 684 7708; fax: +1 919 684 7121.
    • ,
  • Abraham Boskovitz

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Chien-Tsun Kuan

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Charles N. Pegram

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Joanne Ayriss

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Carol J. Wikstrand

      Affiliations

    • Department of Microbiology, Saba University School of Medicine, Saba, Netherlands Antilles
    • ,
  • Anne F. Buckley

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Eric S. Lipp

      Affiliations

    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • James E. Herndon II

      Affiliations

    • Department of Biostatistics, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Roger E. McLendon

      Affiliations

    • Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA
    • ,
  • Darell D. Bigner

      Affiliations

    • Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
    • Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Durham, NC 27710, USA

Received 7 April 2011 ,Revised 17 June 2011 ,Accepted 24 June 2011.

References 

  1. McLendon R, Rosenblum M, Bigner D. In: Russell and Rubinstein's Pathology of Tumors of the Nervous System. 7th ed. London: Hodder Arnold; 2006;p. 1132
  2. Kleihues P, Cavenee W. In: Pathology & Genetics — Tumours of the Nervous System. Lyon: IARC Press; 2000;p. 29–44
  3. Stupp R, Mason W, Bent Mvd, Weller M, Fisher B, Taphoorn M, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–996
  4. Friedman H, Prados M, Wen P, Middlesen T, Schiff D, Abrey L, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009;27:4733–4740
  5. Stupp R, Hegi M, Mason W, Bent Mvd, Taphoorn M, Janzer R, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10:459–466
  6. Vredenburgh J, Desjardins A, Herndon JE, Dowell J, Reardon D, Quinn J, et al. Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res. 2007;13:1253–1259
  7. Vredenburgh J, Desjardins A, Herndon JE, Marcello J, Reardon D, Quinn J, et al. Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol. 2007;25:4722–4729
  8. Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, et al. Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985;313:144–147
  9. Bigner SH, Burger PC, Wong AJ, Werner MH, Hamilton SR, Muhlbaier LH, et al. Gene amplification in malignant human gliomas: clinical and histopathologic aspects. J Neuropathol Exp Neurol. 1988;47:191–205
  10. Wong AJ, Ruppert JM, Bigner SH, Grzeschik CH, Humphrey PA, Bigner DD, et al. Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci U S A. 1992;89:2965–2969
  11. Humphrey P, Wong A, Vogelstein B, Zalutsky M, Fuller G, Archer G, et al. Anti-synthetic peptide antibody reacting at the fusion junction of deletion-mutant epidermal growth factor receptors in human glioblastoma. Proc Natl Acad Sci U S A. 1990;87:4207–4211
  12. Lund-Johansen M, Bjerkvig R, Humphrey PA, Bigner SH, Bigner DD, Laerum OD. Effect of epidermal growth factor on glioma cell growth, migration, and invasion in vitro. Cancer Res. 1990;50:6039–6044
  13. Chin L, Meyerson M, Aldape K, Bigner D, Mikkelsen T, VandenBerg S, et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455:1061–1068
  14. Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, et al. An integrated genomic analysis of human glioblastoma multiforme. Science. 2008;321:1807–1812
  15. Quan A, Barnett G, Lee S, Vogelbaum M, Toms S, Staugaitis S, et al. Epidermal growth factor receptor amplification does not have prognostic significance in patients with glioblastoma multiforme. Int J Oncol Biol Phys. 2005;63:695–703
  16. Shinojima N, Tada K, Shiraishi S, Kamiryo T, Kochi M, Nakamura H, et al. Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme. Cancer Res. 2003;63:6962–6970
  17. Watanabe K, Tachibana O, Sata K, Yonekawa Y, Kleihues P, Ohgaki H. Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol. 1996;6:217–223[discussion 23-4]
  18. Pimentel E. Peptide growth factors. In:  Pimentel E editors. Handbook of growth factors. London: CRC; 1994;p. 85–104
  19. Brandes AA, Franceschi E, Tosoni A, Hegi ME, Stupp R. Epidermal growth factor receptor inhibitors in neuro-oncology: hopes and disappointments. Clin Cancer Res. 2008;14:957–960
  20. Wikstrand CJ, Fung KM, Trojanowski JQ, McLendon RE, Bigner DD. Antibodies and molecular immunology: immunohistochemistry and antigens of diagnostic significance. In:  Bigner DD,  McLendon RE,  Bruner JM editor. Russell and Rubinstein's Pathology of the Nervous System. New York: Oxford University Press; 1998;p. 251–304
  21. Laskin JJ, Sandler AB. Epidermal growth factor receptor: a promising target in solid tumours. Cancer Treat Rev. 2004;30:1–17
  22. Boskovitz A, Wikstrand CJ, Kuan CT, Zalutsky MR, Reardon DA, Bigner DD. Monoclonal antibodies for brain tumour treatment. Expert Opin Biol Ther. 2004;4:1453–1471
  23. Harari PM. Epidermal growth factor receptor inhibition strategies in oncology. Endocr Relat Cancer. 2004;11:689–708
  24. Stragliotto G, Vega F, Stasiecki P, Gropp P, Poisson M, Delattre JY. Multiple infusions of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (EMD 55,900) in patients with recurrent malignant gliomas. Eur J Cancer. 1996;32A:636–640
  25. Faillot T, Magdelenat H, Mady E, Stasiecki P, Fohanno D, Gropp P, et al. A phase I study of an anti-epidermal growth factor receptor monoclonal antibody for the treatment of malignant gliomas. Neurosurgery. 1996;39:478–483
  26. Wersall P, Ohlsson I, Biberfeld P, Collins VP, von Krusenstjerna S, Larsson S, et al. Intratumoral infusion of the monoclonal antibody, mAb 425, against the epidermal-growth-factor receptor in patients with advanced malignant glioma. Cancer Immunol Immunother. 1997;44:157–164
  27. Epenetos AA, Courtenay-Luck N, Pickering D, Hooker G, Durbin H, Lavender JP, et al. 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;290:1463–1466
  28. Brady LW, Miyamoto C, Woo DV, Rackover M, Emrich J, Bender H, et al. Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial. Int J Radiat Oncol Biol Phys. 1992;22:225–230
  29. Kalofonos HP, Pawlikowska TR, Hemingway A, Courtenay-Luck N, Dhokia B, Snook D, et al. Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase. J Nucl Med. 1989;30:1636–1645
  30. Quang TS, Brady LW. Radioimmunotherapy as a novel treatment regimen: 125I-labeled monoclonal antibody 425 in the treatment of high-grade brain gliomas. Int J Radiat Oncol Biol Phys. 2004;58:972–975
  31. Scott AM, Lee FT, Tebbutt N, Herbertson R, Gill SS, Liu Z, et al. A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors. Proc Natl Acad Sci U S A. 2007;104:4071–4076
  32. Wikstrand CJ, Hale LP, Batra SK, Hill ML, Humphrey PA, Kurpad SN, et al. Monoclonal antibodies against EGFRvIII are tumor specific and react with breast and lung carcinomas and malignant gliomas. Cancer Res. 1995;55:3140–3148
  33. Batra SK, Castelino-Prabhu S, Wikstrand CJ, Zhu X, Humphrey PA, Friedman HS, et al. Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene. Cell Growth Differ. 1995;6:1251–1259
  34. Sampson JH, Crotty LE, Lee S, Archer GE, Ashley DM, Wikstrand CJ, et al. Unarmed, tumor-specific monoclonal antibody effectively treats brain tumors. Proc Natl Acad Sci U S A. 2000;97:7503–7508
  35. Yang W, Barth RF, Wu G, Ciesielski MJ, Fenstermaker RA, Moffat BA, et al. Development of a syngeneic rat brain tumor model expressing EGFRvIII and its use for molecular targeting studies with monoclonal antibody L8A4. Clin Cancer Res. 2005;11:341–350
  36. Yang W, Barth RF, Wu G, Kawabata S, Sferra TJ, Bandyopadhyaya AK, et al. Molecular targeting and treatment of EGFRvIII-positive gliomas using boronated monoclonal antibody L8A4. Clin Cancer Res. 2006;12:3792–3802
  37. Ding D, Kanaly C, Bigner D, Cummings T, Herndon JE, Pastan I, et al. Convection-enhanced delivery of free gadolinium with the recombinant immunotoxin MR1-1. J Neurooncol. 2010;98:1–7
  38. Nagane M, Coufal F, Lin H, Bogler O, Cavenee WK, Huang HJ. A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res. 1996;56:5079–5086
  39. Wikstrand CJ, McLendon RE, Friedman AH, Bigner DD. Cell surface localization and density of the tumor-associated variant of the epidermal growth factor receptor, EGFRvIII. Cancer Res. 1997;57:4130–4140
  40. Wikstrand CJ, McLendon RE, Bullard DE, Fredman P, Svennerholm L, Bigner DD. Production and characterization of two human glioma xenograft-localizing monoclonal antibodies. Cancer Res. 1986;46:5933–5940
  41. He X, Archer GE, Wikstrand CJ, Morrison SL, Zalutsky MR, Bigner DD, et al. Generation and characterization of a mouse/human chimeric antibody directed against extracellular matrix protein tenascin. J Neuroimmunol. 1994;52:127–137
  42. CBTRUS . Statistical Report: Primary Brain Tumors in the United States, 2000–2004. Hindsdale, IL: Published by the Central Brain Tumor Registry of the United States; 2008;
  43. Liu L, Backlund LM, Nilsson BR, Grander D, Ichimura K, Goike HM, et al. Clinical significance of EGFR amplification and the aberrant EGFRvIII transcript in conventionally treated astrocytic gliomas. J Mol Med. 2005;83:917–926
  44. Umesh S, Tandon A, Santosh V, Anandh B, Sampath S, Chandramouli BA, et al. Clinical and immunohistochemical prognostic factors in adult glioblastoma patients. Clin Neuropathol. 2009;28:362–372
  45. Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–145
  46. Zalutsky MR, Archer GE, Garg PK, Batra SK, Bigner DD. Chimeric anti-tenascin antibody 81C6: increased tumor localization compared with its murine parent. Nucl Med Biol. 1996;23:449–458
  47. Reist CJ, Archer GE, Kurpad SN, Wikstrand CJ, Vaidyanathan G, Willingham MC, et al. Tumor-specific anti-epidermal growth factor receptor variant III monoclonal antibodies: use of the tyramine-cellobiose radioiodination method enhances cellular retention and uptake in tumor xenografts. Cancer Res. 1995;55:4375–4382
  48. Reist CJ, Batra SK, Pegram CN, Bigner DD, Zalutsky MR. In vitro and in vivo behavior of radiolabeled chimeric anti-EGFRvIII monoclonal antibody: comparison with its murine parent. Nucl Med Biol. 1997;24:639–647
  49. Luwor RB, Johns TG, Murone C, Huang HJ, Cavenee WK, Ritter G, et al. Monoclonal antibody 806 inhibits the growth of tumor xenografts expressing either the de2-7 or amplified epidermal growth factor receptor (EGFR) but not wild-type EGFR. Cancer Res. 2001;61:5355–5361
  50. Johns TG, Adams TE, Cochran JR, Hall NE, Hoyne PA, Olsen MJ, et al. Identification of the epitope for the epidermal growth factor receptor-specific monoclonal antibody 806 reveals that it preferentially recognizes an untethered form of the receptor. J Biol Chem. 2004;279:30375–30384
  51. Jungbluth AA, Stockert E, Huang HJ, Collins VP, Coplan K, Iversen K, et al. A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor. Proc Natl Acad Sci U S A. 2003;100:639–644
  52. Johns TG, Stockert E, Ritter G, Jungbluth AA, Huang HJ, Cavenee WK, et al. Novel monoclonal antibody specific for the de2-7 epidermal growth factor receptor (EGFR) that also recognizes the EGFR expressed in cells containing amplification of the EGFR gene. Int J Cancer. 2002;98:398–408
  53. Hall WA, Fodstad O. Immunotoxins and central nervous system neoplasia. J Neurosurg. 1992;76:1–12
  54. Costantini D, McLarty K, Lee H, Done S, Vallis KA, Reilly RM. Anti-tumor effects and normal tissue toxicity of 111In-NLS-trastuzumab in mice bearing HER-positive human breast cancer xenografts. J Nucl Med. 2010;51:1084–1091
  55. Hens M, Vaidyanathan G, Welsh P, Zalutsky MR. Labeling internalizing anti-epidermal growth factor receptor variant III monoclonal antibody with 177Lu: in vitro comparison of acyclic and macrocyclic. ligands. Nucl Med Biol. 2009;36:117–128
  56. Davies GC, Ryan PE, Rahman L, Zajac-Kaye M, Lipkowitz S. EGFRvIII undergoes activation-dependent downregulation mediated by the Cbl proteins. Oncogene. 2006;25:6497–6509
  57. Vaidyanathan G, Alston KL, Bigner DD, Zalutsky MR. Nɛ-(3-[*I]iodobenzoyl)-Lys5-Nαmaleimido-Gly1-GEEEK ([*I]IB-Mal-D-GEEEK): A radioiodinated prosthetic group containing negatively charged D-glutamates for labeling internalizing monoclonal antibodies. Bioconjug Chem. 2006;17:1085–1092
  58. Foulon CF, Reist CJ, Bigner DD, Zalutsky MR. Radioiodination via d-amino acid peptide enhances cellular retention and tumor xenograft targeting of an internalizing anti-epidermal growth factor receptor variant III monoclonal antibody. Cancer Res. 2000;60:4453–4460
  59. Vaidyanathan G, Affleck DJ, Bigner DD, Zalutsky MR. Improved xenograft targeting of tumor-specific anti-epidermal growth factor receptor variant III antibody labeled using N-succinimidyl 4-guanidinomethyl-3-iodobenzoate. Nucl Med Biol. 2002;29:1–11

☆ This study was supported by the following NIH grants: NINDS 5P50 NS20023, NCI CA42324, NCI 5P50 CA108786 and NCI R37 CA011898.

PII: S0969-8051(11)00153-3

doi: 10.1016/j.nucmedbio.2011.06.005

Nuclear Medicine and Biology
Volume 39, Issue 1 , Pages 23-34 , January 2012

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