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Immunotoxins for Glioma Therapy

  • Chapter
High-Grade Gliomas

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

Targeting cancer cells with an immunotoxin represents a novel therapeutic approach. Several immunotoxins composed of a ligand or antibody and truncated bacterial toxins are in clinical development to treat various cancers including glioblastoma multiforme (GBM). GBM is an infiltrative tumor that defies a “ecomplete surgical resection”e invariably recurring most often at the site of resection. A number of local therapies are being explored. One approach is to identify unique or over-expressed cell surface receptors on GBM cells and targeting them with a receptor-specific immunotoxin. We have identified over-expression of a receptor for an immune regulatory cytokine, interleukin-13 (IL-13) on human malignant glioma cell lines, primary brain tumor cell cultures, and tumor tissues. The targeting of IL-13 receptors (IL-13R) with a recombinant fusion protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (IL 13-PE3 8QQR or IL-13-PE38, referred to here as IL 13-PE) demonstrated apotent and specific cell-killing of GBM cells in vitro. Normal brain cells, immune cells, and endothelial cells devoid of the unique IL-13R chain were not susceptible to immunotoxin cell killing activity. Direct injection of IL13-PE into subcutaneous (sc) or intracranial human GBM tumors in nude mice resulted in complete and durable regression of tumors. IL13-PE delivered through intravenous (iv) and intraperitoneal (ip) routes of administration also reduced sc tumor burden with fewer complete responses (CR). High doses of systemic (up to 50 μg/kg) or intracerebral (up to 100 μg/mL) IL13-PE were well tolerated in mice and rats, respectively without evidence of gross or microscopic necrosis.

Based on these encouraging preclinical results, four phase I and II clinical trials were initiated to investigate the safety, toxicity, and optimal convection-enhanced delivery (CED) of IL13-PE to patients with recurrent malignant gliomas; patients had already undergone standard therapy including surgery, radiation, and chemotherapy. CED uses a positive pressure to generate a pressure gradient that optimizes distribution of the macromolecule within tumor and peritumoral regions. A total of 97 patients were treated with IL13-PE in these studies. CED of IL13-PE into solid tumor component as well as the surrounding brain tissues felt to be at risk for residual infiltrating tumor before and after tumor resection, respectively was fairly well tolerated in terms of safety profile. Histological antitumor effects have been observed at drug concentrations of 0.5, 1.0 and 2.0 μg/mL without apparent increased antitumor activity at higher concentrations. Duration of infusions up to 7 d was fairly well tolerated. A randomized worldwide phase III clinical trial (PRECISE, phase III Randomized Evaluation of Convection Enhanced Delivery of IL 13-PE3 8QQR with Survival Endpoint) is currently recruiting patients with recurrent supratentorial GBM at first recurrence to evaluate overall survival duration, safety, and quality-of-life of patients treated by tumor resection followed by peritumoral IL13-PE infusion vs Gliadel® Wafer placement.

The views presented in this article do not necessarily reflect those of the Food and Drug Administration.

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References

  1. Kawakami K, Aggarwal BB, Puri RK. eds. Cytotoxins and Immunotoxins for Cancer Therapy: Clinical Applications. New York: Taylor and and Francis CRC Press;2004.

    Google Scholar 

  2. Kreitman RJ. Immunotoxin in cancer therapy. Curr Opin Immunol 1999;11:570–578.

    Article  PubMed  CAS  Google Scholar 

  3. Brandes AA, Basso U, Pasetto LM, Ermani B. New strategy developments in brain tumor therapy. CurrPharm Design 2001;7:1553–1580.

    Article  CAS  Google Scholar 

  4. Basso U, Ermani B, Vastola F, Brandes AA. Non-cytotoxic therapies for malignant glioma. J Neuro-Oncol 2002;58:57–69.

    Article  Google Scholar 

  5. Amlot PL, Stone M J, Cunnigham D, Fay J, Newman J, Collins R, May R, McCarthy M, Richardson J, Ghetie V, Ramilo O, Thorpe PE, Uhr JW, Vitetta ES. A phase I study of anti-D22-deglycosylated Ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. Blood 1993;82:2624–2633.

    PubMed  CAS  Google Scholar 

  6. Reiter Y. Recombinant immunotoxins in targeted cancer therapy. Adv Cancer Res 2001;81:93–124.

    PubMed  CAS  Google Scholar 

  7. Laske DW, Ilercil O, Akbasak A, Youle RJ, Oldfield E H. Efficacy of direct intratumoral therapy with targeted protein toxins for solid human gliomas in nude mice. J Neurosurg 1994;80:520–526.

    Article  PubMed  CAS  Google Scholar 

  8. Husain SR, Behari N, Kreitman RJ, Pastan I, Puri RK. Complete regression of established human glioblastoma tumor xenograft by interleukin-4 toxin therapy. Cancer Res 1998;58:3649–3653.

    PubMed  CAS  Google Scholar 

  9. Husain SR, Kreitman RJ, Pastan I, Puri RK. Interleukin-4 receptor directed cytotoxin therapy of AIDS-associated Kaposi’es sarcoma tumors in xenograft model. Nature Med 1999;5:817–822.

    Article  PubMed  CAS  Google Scholar 

  10. Husain SR, Puri RK. Interleukin-13 fusion cytotoxin as a potent targeted drug for AIDS-Kaposi’es sarcoma xenograft. Blood 2000;95:3506–513.

    PubMed  CAS  Google Scholar 

  11. Vallera DA, Li C, Jin N, Panoskaltsis-Mortari A, Hall WA. Targeting urokinase-type plasminogen activator receptor on human glioblastoma tumors with diphtheria toxin fusion protein DTAT. J Natl Cancer Inst 2002;94:597–606.

    PubMed  CAS  Google Scholar 

  12. Li C, Hall WA, Jin N, Panoskaltsis-Mortari A, Vallera DA. Targeting glioblastoma multiforme with an IL-13/diphtheria toxin fusion protein in vitro and in vivo in nude mice. Protein Eng 2002;15:419–427.

    Article  PubMed  Google Scholar 

  13. Kawakami M, Kawakami K, Puri RK, Interleukin-4-Pseudomonas exotoxin chimeric protein for malignant glioma therapy. J Neuro-Oncol 2003;65:15–25.

    Article  Google Scholar 

  14. Pai LH, Wittes R, Setser A, Willingham MC, Pastan I. Treatment of advanced solid tumors with immunotoxin LMB-1:An antibody linked to Pseudomonas exotoxin. Nature Med 1996;2:350–353.

    Article  PubMed  CAS  Google Scholar 

  15. Kreitman RJ, Wilson WH, White JD. Stetler-Stevenson M, Jaffe E, Waldman TA, Pastan I. Phase I trial ofrecombinant immunotoxin Anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol 2000;8:1622–1636.

    Google Scholar 

  16. Kreitman RJ, Wilson WH, Robbins D. Margulis I, Stetler-Stevenson M, Waldman TA, Pastan I. Responses in refractory hairy cell leukemia to a recombinant immunotoxin. Blood 1999;94:3340–3348.

    PubMed  CAS  Google Scholar 

  17. Stone MJ, Sausville EA, Fay JW, et al. A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in-patients with B-cell lymphoma. Blood 1996;88:1188–1197.

    PubMed  CAS  Google Scholar 

  18. Hesketh P, Caguioa P, Koh H, et al. Clinical activity of a cytotoxic fusion protein in the treatment of cutaneous T-cell lymphoma. Blood 1993;11:1682–1690.

    CAS  Google Scholar 

  19. LeMaistre CF, Saleh MN, Kuzel TM, et al. Phase 1 trial of ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2. Blood 1998;91:399–405.

    PubMed  CAS  Google Scholar 

  20. Pai LH, Wittes R, Setser A, Willingham MC, Pastan I. Treatment of advanced solid tumors with immunotoxin LMB-1: an antibody linked to Pseudomonas exotoxin. Nature Med 1996;2:350–353.

    Article  PubMed  CAS  Google Scholar 

  21. Chaudhary VK, Queen C, Junghans RP, Waldmann T A, Fitzgerald DJ, Pastan I. A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin. Nature 1989;339:394–397.

    Article  PubMed  CAS  Google Scholar 

  22. Kreitman RJ, Pastan I. Targeting Pseudomonas exotoxin to hematological malignancies Semin Cancer Biol 1995;6:297–306.

    Article  CAS  Google Scholar 

  23. Pastan I. Immunotoxins containing Pseudomonas exotoxin A: a short history. Cancer Immunol Immunother 2003;52:338–341.

    PubMed  Google Scholar 

  24. Kreitman RJ, Wilson WH, Bergeron K, et al. Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy resistant hairy-cell leukemia. N Eng J Med 2001;345:241–247.

    Article  CAS  Google Scholar 

  25. Chawdhury PS, Viner JL, Beers R, Pastan I. Isolation of high affinity stable single chain Fv specific for mesothelin from DNA-immunized mice by phage display and construction of a recombinant immunotoxin with antitumor activity. Proc Natl Acad Sci USA 1998;95:669–674.

    Article  Google Scholar 

  26. Olsen E, Duvic M, Frankel A, et al. Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. J Clin Oncol 2001;19:376–388.

    PubMed  CAS  Google Scholar 

  27. Liu TF, Chen KA, Ramage JG, Willingham MC, Thorburn AM, Frankel AE. A diphtheria toxin-epidermal growth factor fusion protein is cytotoxic to human glioblastoma multiforme cells. Cancer Res 2003;63:1834–1837.

    PubMed  CAS  Google Scholar 

  28. Foss FM, Saleh MN, Kruger JG, Nicholas JC, Murphy JR Diphtheria toxin fusion proteins. In: Frankel AE, ed. Berlin: Springer-Verlag. Clinical Applications of Immunotoxins. Curr Topics Microbiol Immunol 1998;234:63–81.

    Google Scholar 

  29. Lorimer IA, Keppler-Hafkemeyer A, Beers RA, Pegram CN, Bigner DD, Pastan I. Immunotoxins that target an oncogenic mutant epidermal growth factor receptor expressed in human tumors. Clin Cancer Res 1995;1:859–864.

    PubMed  CAS  Google Scholar 

  30. Piccaluga PP, Martinelli G, Rondoni M, Malagola M, Gaitani S, Visani G, B accarani M. First experience with gemtuzumab ozogamicin plus cytarabine as continuous infusion for elderly acute myeloid leukaemia patients. Leukemia Res 2004;28:987–990.

    Article  CAS  Google Scholar 

  31. Sievers EL. Antibody-targeted chemotherapy of acute myeloid leukemia using gemtuzumab ozogamicin (Mylotarg). Blood Cells Molecules Diseases 2003;31:7–10.

    Article  CAS  Google Scholar 

  32. Schnell R, Borchmann P, Staak JO, Ghetie V, Vitetta ES, Engert A. Clinical evaluation of ricin A-chain immunotoxins in patients with Hodgkin’es lymphoma. Ann Oncol 2003;14:729–736.

    Article  PubMed  CAS  Google Scholar 

  33. National Center for Health Statistics for the United States, 1994. Washington, DC: Public Health Service; 1997.

    Google Scholar 

  34. Laske DW, Youle RJ, Oldfield EH. Tumor regression with regional distribution of the targeted toxin TF-CRM107 in patients with malignant brain tumors. Nature Med 1997;3:1362–1368.

    Article  PubMed  CAS  Google Scholar 

  35. Oldfield E H, Youle RJ. Immunotoxin for brain tumor therapy. Curr Opin Microbiol 1998;234:9–114.

    Google Scholar 

  36. Weaver M, Laske DW. Transferrin receptor ligand-targeted toxin conjugate (TfCRM107) for therapy of malignant gliomas. J Neuro-Oncol 2003;65:3–14.

    Article  Google Scholar 

  37. Phillips PC, Levow C, Caterall M, Colvin OM, Pastan I, Brem H. Transforming growth factor-α-Pseudomonas exotoxin fusion protein (TGF-PE38) treatment of subcutaneous and intracranial human glioma and medulloblastoma xenografts in athymic mice. Cancer Res 1994;54:1008–1015.

    PubMed  CAS  Google Scholar 

  38. Sampson JH, Akabani G, Archer GE, et al. Progress report of aPhase I study of the intracerebral microinfusion of a recombinant chimeric protein composed of transforming growth factor (TGF)-α and a mutated form of the Pseudomonas exotoxin termed PE38 (TP-38) for the treatment of malignant brain tumors. J Neuro-Oncol 2003;65:27–35.

    Article  Google Scholar 

  39. Rustamzadeh E, Li CB, Doumbia S, Hall WA, Vallera DA. Targeting the over-expressedurokinase-type plasminogen activator receptor on glioblastoma multiforme. J Neuro-Oncol 2003;65:63–75.

    Article  Google Scholar 

  40. Todhunter DA, Hall WA, Rustamzadeh E, Shu YQ, Doumbia SO, Vallera DA. A bispecific immunotoxin (DTAT13) targeting human IL-13 receptor (IL-13R) and urokinase-type plasminogen activator receptor (uPAR) in a mouse xenograft model. Protein Engg Design Select 2004;17:157–164.

    Article  CAS  Google Scholar 

  41. Rand RW, Kreitman RJ, Patronas N, Varricchio F, Pastan I, Puri RK. Intratumoral administration of recombinant circularly permuted interleukin-4-Pseudomonas exotoxin inpatients with high grade glioma. Clin Cancer Res 2000;6:2157–2165.

    PubMed  CAS  Google Scholar 

  42. Weber F, Asher A, Bucholz R, et al. Safety, tolerability, and tumor response of IL-4-Pseudomonas exotoxin (NBI-30010) in patients with recurrent malignant glioma J. Neuro-Oncol 2003;64:125–137.

    Google Scholar 

  43. Rainov NG, Heidecke V. Long term survival in a patient with recurrent malignant glioma treated with intratumoral infusion of an IL4-targeted toxin (NBI-3001). J Neuro-Oncol 2004;66:197–201.

    Article  CAS  Google Scholar 

  44. Debinski W, Obiri NI, Powers SK, Pastan I, Puri RK. Human glioma cells overexpress receptors for interleukin 13 and are extremely sensitive to a novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin. Clin Cancer Res 1995;1:1253–1258.

    PubMed  CAS  Google Scholar 

  45. Joshi BH, Plautz GE, Puri RK. Interleukin-13 receptor α chain: a novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Res 2000;60:1168–1172.

    PubMed  CAS  Google Scholar 

  46. Husain SR, Puri RK. Interleukin-13receptor-directed cytotoxin for malignant glioma therapy: from bench to bedside. J Neuro-Oncol 2003;65:37–48.

    Article  Google Scholar 

  47. Kuzel T, Smith II J, Urba W, Fox B, Moudgil T, Strauss L, Joshi B, Puri R. IL13-PE38QQR cytotoxicity in advanced renal cell carcinoma (RCC): phase 1 and pharmacokinetics study. San Francisco: American Society of Clinical Oncology (ASCO);2002.

    Google Scholar 

  48. Zurawski G, De Vries JE. Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today 1994;15:19–26.

    Article  PubMed  CAS  Google Scholar 

  49. Punnonen J, Aversa G, Cocks BG, et al. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc Natl Acad Sci USA 1993;90:3730–3734.

    Article  PubMed  CAS  Google Scholar 

  50. Minty A, Chalon P, Derocq J-M, et al. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 1993;362:248–250.

    Article  PubMed  CAS  Google Scholar 

  51. Defrance T, Carayon P, Billian G, et al. Interleukin-13 is a B cell stimulatory factor. J Exp Med 994;179:135–143.

    Google Scholar 

  52. Herber J-M, Savi P, Laplace MC, et al. IL-4 and IL-13 exhibit comparable abilities to reduce pyrogeninduced expression of procoagulant activity in endothelial cells and monocytes. FEBS Lett 1993;328:268–270.

    Article  Google Scholar 

  53. Obiri NI, Debinski W, Leonard WJ, Puri RK. Receptor for interleukin 13. Interaction with interleukin 4 by a mechanism that does not involve the common γ chain shared by receptors for interleukin 2, 4, 7, 9, and 15. J Biol Chem 1995;270:8797–8804.

    Article  PubMed  CAS  Google Scholar 

  54. Husain SR, Obiri NI, Gill P, et al. Receptors for interleukin 13 on AIDS-associated Kaposi’es sarcoma cells serves as a new target for a potent Pseudomonas exotoxin-based chimeric toxin protein. Clin Cancer Res 1997;3:151–156.

    PubMed  CAS  Google Scholar 

  55. Obiri NI, Leland P, Murata T, Debinski W, Puri RK. The IL-13 receptor structure differs on various cell types and may share more than one component with IL-4 receptor complex. J Immunol 1997;158:756–764.

    PubMed  CAS  Google Scholar 

  56. Miloux B, Laurent P, Bonnin O, Luker J, Caput D, Vita N, Ferrara P. Cloning of the human IL-13Ralpha1 chain and reconstitution with the IL-4R alpha of functional IL-4/IL-13 receptor complex. FEBS Lett 1997;401:163–166.

    Article  PubMed  CAS  Google Scholar 

  57. Hilton DJ, Zhang JG, Metcalf D, Alexander WS, Nicola NA, Wilson TA. Cloning and characterization of binding subunits of the interleukin 13 receptor that is also a component of the interleukin 4 receptor. Proc Natl Acad Sci USA 1996;93:497–501.

    Article  PubMed  CAS  Google Scholar 

  58. Aman MJ, Tayebi N, Obiri NI, Puri RK, Modi WS, Leonard W. cDNA cloning and characterization of the human interleukin 13 receptor α chain. J Biol Chem 1996;271:29,265–29,670.

    Article  PubMed  CAS  Google Scholar 

  59. Murata T, Obiri NI, Puri RK. Structure and signal transduction through interleukin-4 and interleukin-13 receptors, Int J Mol Med 1998;1:551–557.

    PubMed  CAS  Google Scholar 

  60. Caput D, Laurent P, Kaghad M, et al. Cloning and characterization of a specific interleukin (IL)-13 binding protein structurally related to IL-5 receptor α chain. J Biol Chem 1996;271:16,921–16,926.

    Article  PubMed  CAS  Google Scholar 

  61. Kawakami M, Leland P, Kawakami K, Puri RK. Mutation and functional analysis of IL-13 receptors in human malignant glioma cells. Oncol Res 2001;12:459–467.

    PubMed  CAS  Google Scholar 

  62. Donaldson DD, Whitters MJ, Fitz LJ, et al. The murine IL-13 receptor a2: Molecular cloning, characterization, and comparison with murine IL-13 receptor α1. J Immunol 1998;161:2317–2324.

    PubMed  CAS  Google Scholar 

  63. Murata T, Obiri NI, Debinski W, Puri RK. Structure of IL-13 receptor: analysis of subunit composition in cancer and immune cells. BiochemBiophys Res Comm 1997;238:90–94.

    Article  CAS  Google Scholar 

  64. Joshi BH, Husain SR, Puri RK. Preclinical studies with IL-13PE3 8QQR for therapy of malignant glioma. Drug News Perspect 2000;13:599–605.

    Article  PubMed  CAS  Google Scholar 

  65. Schnyder B, Lugi S, Fenf N, et al. Interleukin-4 (IL-4) and IL-13 bind to a shared heterodimeric complex on endothelial cells mediating vascular cell adhesion molecule-1 induction in the absence of the common γ chain. Blood 1996;87:4286–4295.

    PubMed  CAS  Google Scholar 

  66. Kawakami K, Kawakami M, Snoy P, Husain SR, Puri RK. In vivo overexpression of IL-13 receptor α2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice. J Ex Med 2001;196:1743–1754.

    Article  Google Scholar 

  67. Kawakami K, Husain SR, Bright RK, Puri RK. Gene transfer of interleukin 13 receptor α2 chain dramatically enhances the antitumor effect of IL-13 receptor-targeted cytotoxin in human prostate cancer xenografts. Cancer Gene Ther 2001;8:861–868.

    Article  PubMed  CAS  Google Scholar 

  68. Vita N, Lefort S, Laurent P, Caput D, Ferrara P. Characterization and comparison of the interleukin 13 receptor with the interleukin 4 receptor on several cell types. J Biol Chem 1995;270:3512–3517.

    Article  PubMed  CAS  Google Scholar 

  69. Kawakami K, Taguchi J, Murata T, Puri RK. The interleukin-13 receptor α2 chain: an essential component for binding and internalization but not interleukin-13-induced signal transduction through the STAT6 pathway. Blood 2001;97:2673–2679.

    Article  PubMed  CAS  Google Scholar 

  70. Joshi BH, Husain SR, Leland P, Puri RK. Interleukin-13 receptors and development of IL-13-Pseudomonas exotoxin for human cancer therapy. In: Aggarwal BB, Kawakami K, Puri RK, eds. Cytotoxins and Immunotoxins for Cancer Therapy: Clinical applications. New York: Taylor and Frances CRC Press; 2004:45–69.

    Google Scholar 

  71. Kawakami K, Joshi BH, Puri RK. Sensitization of cancer cells to interleukin-13-Pseudomonas exotoxininduced cell death by gene transfer of interleukin-13 achain. Hum Gene Ther 2000;11:1829–1835.

    Article  PubMed  CAS  Google Scholar 

  72. Kawakami K, Kawakami M, Puri RK. Cytokine receptor as a sensitizer for targeted cancer therapy. Anticancer Drugs 2002;13:693–699.

    Article  PubMed  CAS  Google Scholar 

  73. Pastan I, Chaudhary VK, FitzGerald D. Recombinant toxins as novel therapeutic agents. Annu Rev Biochem 1992;61:331–354.

    Article  PubMed  CAS  Google Scholar 

  74. Joshi BH, Kawakami K, Leland P, Puri RK. Heterogeneity in interleukin-13 receptor expression and subunit structure in squamous cell carcinoma of head and neck: Differential sensitivity of to chimeric fusion proteins comprised of interleukin-13 and a mutated form of Pseudomonas exotoxin. Clin Cancer Res 2002;8:1948–1956.

    PubMed  CAS  Google Scholar 

  75. Debinski W, Obiri NI, Pastan I, Puri RK. A novel chimeric protein composed of interleukin 13 and Pseudomonas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4. J Biol Chem 1995;270:16,775–16,780.

    Article  PubMed  CAS  Google Scholar 

  76. Husain SR, Joshi BH, Puri RK. Interleukin-13 Receptors as a unique target for anti-glioblastoma therapy. Int J Cancer 2001;92:168–175.

    Article  PubMed  CAS  Google Scholar 

  77. Husain SR, Kawakami M, Kawakami K, Snoy PJ, Puri RK. Continuous intraperitoneal infusion increases the efficacy and safety of IL-13 toxin in elimination of established human glioblastoma tumor xenografts. Proc Amer Assn Cancer Res 2001;42:777.

    Google Scholar 

  78. Zurawski SM, Chomarat P, Djossou O, et al. The primary binding subunit of the human interleukin-4 receptor is also a component of the interleukin-13 receptor. J Biol Chem 1995;270:13,869–13,878.

    Article  PubMed  CAS  Google Scholar 

  79. Husain SR, Oshima Y, Gokhale PC, Kasid UN, Puri RK. Pre-clinical safety evaluation of recombinant interleukin 13-pseudomonas exotoxin (IL13-PE38) for targeted cancer therapy. Proc Amer Assoc Cancer Res 2003;44(1st Ed.): 1257 and 44(2nd Ed.): 1092.

    Google Scholar 

  80. Weingart J, Grossman SA, Bohan E, Fisher JD, Strauss L, Puri RK. Phase I/II study of interstitial infusion of IL13-PE38QQR cytotoxin in recurrent malignant glioma. Washington, DC:First Quadrennial meeting-World Federation of Neuro-Oncology. November 15–17, 2001.

    Google Scholar 

  81. Weingart J, Strauss LC Grossman SA, Markett J, Tatter S, Fisher JD, Fleming CK, Puri RK. Phase I/II study: Intra-tumoral infusion of IL13-PE38QQR cytotoxin for recurrent supratentorial malignant glioma. Neurooncology 2002;4:379.

    Google Scholar 

  82. Weingart J, Markert J, Tatter S, et al. Determination of toxicities and maximum tolerated dose (MTD) of intratumoral infusion of IL13-PE38QQR cytotoxin in patients with recurrent supratentorial malignant glioma: a phase I/II study. Proc Am Soc Clin Oncol 2003;22:101.

    Google Scholar 

  83. Prados MD, Lang FF, Strauss L, et al. Intratumoral and intracerebral microinfusion of IL13-PE38QQR cytotoxin: Phase I/II study of pre-and post-resection infusions in recurrent resectable malignant glioma. Proc Am Soc Clin Oncol 2002;21(2):69b.

    Google Scholar 

  84. Lang F, Kunwar S, Strauss L, et al. A clinical study of convection-enhanced delivery of IL13-PE38QQR cytotoxin pre-and post-resection of recurrent GBM. Chicago: American Society of Neuro-Oncologists; April, 2002.

    Google Scholar 

  85. Prados MD, Lang FF, Sherman JW, et al. Convection-enhanced delivery (CED) by positive pressure infusion for intra-tumoral and peri-tumoral administration of IL13-PE38QQR a recombinant tumor-targeted cytotoxin in recurrent malignant glioma. Neuro-oncology 2002;4:S78.

    Google Scholar 

  86. Prados MD, Lang FF, Strauss LC et al. Pre-and Post-resection interstitial infusion of IL13-PE38QQR cytotoxin: Phase I study in recurrent resectable malignant glioma. Washington, DC: Quadrennial Meeting of the World Federation of Neuro-Oncology; Nov 15–18, 2001.

    Google Scholar 

  87. Kunwar S. Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: presentation of interim findings from ongoing phase 1 studies. In: Westphal M, Tonn JC, Ram, ed. New York: Springer Wien. Local therapies for glioma: present status and future development, Acta Neurochir Suppl 2003;88:105–111.

    Google Scholar 

  88. Kunwar S, Prados MD, Lang FF, et al. Intratumoral and peritumoral convection-enhanced delivery of IL13-PE38QQR, a recombinant tumor-targeted cytotoxin in a recurrent malignant glioma phase I trial. J Neurosurg 2003;98:697.

    Google Scholar 

  89. Kunwar S, Prados M, Lang F, et al. Intracerebral convection-enhanced delivery (CED) of IL13-PE38QQR, a recombinant tumor-targeted cytotoxin, in recurrent malignant glioma: a phase I trial. Neuro-oncology 2003;5:387.

    Google Scholar 

  90. Kunwar S, Prados M, Lang F, et al. Pre-and post-operative infusion of IL13-PE38QQR cytotoxin by convectionenhanced delivery (CED) in recurrent malignant glioma: a phase I study. Proc Am Soc Clin Oncol 2003;22:119.

    Google Scholar 

  91. Ram Z, Barnett G, Vogelbaum M, et al. Pre-operative infusion of IL13-PE38QQR cytotoxin by convectionenhanced delivery (CED) in recurrent malignant glioma: a phase I/II study. Proc Am Soc Clin Oncol 2003;22:101.

    Google Scholar 

  92. Sampson JH, Friedman AH, Reardon DA, et al. Convection Enhanced Delivery of IL13-PE38QQR in Malignant Glioma: Effect of Catheter Placement on Drug Distribution. Orlando, FL: American Association of Neurological Surgeons Annual Meeting; 2004.

    Google Scholar 

  93. Kawakami M, Kawakami K, Abe M, Puri RK. Analysis of interleukin-13 receptor α2 expression in human pediatric brain tumors. Cancer 2004;101:1036–1042.

    Article  PubMed  CAS  Google Scholar 

  94. Brinkmann U, Keppler-Hafkemeyer A, Hafkemeyer P. Recombinant immunotoxins for cancer therapy. Exp Opin Biol Ther 2001;1:693–702.

    Article  CAS  Google Scholar 

  95. Kawakami M, Kawakami K, Puri RK. Intratumor administration of interleukin 13 receptortargeted cytotoxin induces apoptotic cell death in human malignant glioma tumor xenografts. Mol Cancer Ther 2002;1:999–1007.

    PubMed  CAS  Google Scholar 

  96. Kim DK, Uttley B, Bell BA, Marsh HT, Moore AJ. Comparison of rates of infection of two methods of emergency ventricular damage. J Neurol Neurosurg Psych 1995;58:444–446.

    CAS  Google Scholar 

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  1. Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, FDA, Bethesda, MD

    Syed Rafat Husain & Raj K. Puri

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  1. Syed Rafat Husain
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  2. Raj K. Puri
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  1. Department of Neurological Surgery Cleveland Clinic Foundation, Brain Tumor Institute, Cleveland, OH

    Gene H. Barnett MD

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Husain, S.R., Puri, R.K. (2007). Immunotoxins for Glioma Therapy. In: Barnett, G.H. (eds) High-Grade Gliomas. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-59745-185-7_19

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  • DOI: https://doi.org/10.1007/978-1-59745-185-7_19

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-511-8

  • Online ISBN: 978-1-59745-185-7

  • eBook Packages: MedicineMedicine (R0)

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