Skip to main content
SpringerLink
Log in

Neurosurgical Delivery of Chemotherapeutics, Targeted Toxins, Genetic and Viral Therapies in Neuro-Oncology

  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Local delivery of biologic agents, such as gene and viruses, has been tested preclinically with encouraging success, and in some instances clinical trials have also been performed. In addition, the positive pressure infusion of various therapeutic agents is undergoing human testing and approval has already been granted for routine clinical use of biodegradable implants that diffuse a chemotherapeutic agent into peritumoral regions. Safety in glioma patients has been shown, but anticancer efficacy needs additional refinements in the technologies employed. In this review, we will describe these modalities and provide a perspective on needed improvements that should render them more successful.

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. Bartus RT, Elliott PJ, Dean RL, Hayward NJ, Nagle TL, Huff MR, Snodgrass PA, Blunt DG: Controlled modulation of BBB permeability using the bradykinin agonist, RMP-7. Exp Neurol 142: 14–28, 1996

    CAS  PubMed  Google Scholar 

  2. Bobo RH, Laske DW, Akbasak A, Morrison PF, Dedrick RL, Oldfield EH: Convection-enhanced delivery of macromolecules in the brain. Proc Natl Acad Sci USA 91: 2076–2080, 1994

    CAS  PubMed  Google Scholar 

  3. Kroll RA, Pagel MA, Muldoon LL, Roman-Goldstein S, Neuwelt EA: Increasing volume of distribution to the brain with interstitial infusion: dose, rather than convection, might be the most important factor. Neurosurgery 38: 746–752;discussion 752–754, 1996

    CAS  PubMed  Google Scholar 

  4. Bruce JN, Falavigna A, Johnson JP, Hall JS, Birch BD, Yoon JT, Wu EX, Fine RL, Parsa AT: Intracerebral clysis in a rat glioma model. Neurosurgery 46: 683–691, 2000

    CAS  PubMed  Google Scholar 

  5. Broaddus WC, Gillies GT, Kucharczyk J: Minimally invasive procedures. Advances in image-guided delivery of drug and cell therapies into the central nervous system. Neuroimaging Clin N Am 11: 727–735, 2001

    CAS  PubMed  Google Scholar 

  6. Chiocca EA: Gene therapy: a primer for neurosurgeons. Neurosurgery 53: 364–373;discussion 373, 2003

    PubMed  Google Scholar 

  7. Brem H, Piantadosi S, Burger PC, Walker M, Selker R, Vick NA, Black K, Sisti M, Brem S, Mohr G, et al.: Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group. Lancet 345: 1008–1012, 1995

    CAS  PubMed  Google Scholar 

  8. Valtonen S, Timonen U, Toivanen P, Kalimo H, Kivipelto L, Heiskanen O, Unsgaard G, Kuurne T: Interstitial chemotherapy with carmustine-loaded polymers for high-grade gliomas: a randomized double-blind study. Neurosurgery 41: 44–48; discussion 48–49, 1997

    CAS  PubMed  Google Scholar 

  9. Westphal M, Hilt DC, Bortey E, Delavault P, Olivares R, Warnke PC, Whittle IR, Jaaskelainen J, Ram Z: A phase 3 trial of local chemotherapy with biodegradable carmustine (BCNU)wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-oncol 5: 79–88, 2003

    CAS  PubMed  Google Scholar 

  10. Fung LK, Ewend MG, Sills A, Sipos EP, Thompson R, Watts M, Colvin OM, Brem H, Saltzman WM: Pharmacokinetics of interstitial delivery of carmustine, 4-hydroperoxycyclophosphamide, and paclitaxel from a biodegradable polymer implant in the monkey brain. Cancer Res 58: 672–684, 1998

    CAS  PubMed  Google Scholar 

  11. Pietronigro D, Drnovsky F, Cravioto H, Ransohoffi J: DTI-015 produces cures in T9 gliosarcoma. Neoplasia 5: 17–22, 2003

    CAS  PubMed  Google Scholar 

  12. Hassenbusch SJ, Nardone EM, Levin VA, Leeds N, Pietronigro D: Stereotactic injection of DTI-015 into recurrent malignant gliomas: phase I/II trial. Neoplasia 5: 9–16, 2003

    CAS  PubMed  Google Scholar 

  13. Mardor Y, Roth Y, Lidar Z, Jonas T, Pfeffier R, Maier SE, Faibel M, Nass D, Hadani M, Orenstein A, Cohen JS, Ram Z: Monitoring response to convection-enhanced taxol delivery in brain tumor patients using diffiusion-weighted magnetic resonance imaging. Cancer Res 61: 4971–4973, 2001

    CAS  PubMed  Google Scholar 

  14. Hall WA: Immunotoxin treatment of brain tumors. Methods Mol Biol 166: 139–154, 2001

    CAS  PubMed  Google Scholar 

  15. Laske DW, Morrison PF, Lieberman DM, Corthesy ME, Reynolds JC, Stewart-Henney PA, Koong SS, Cummins A, Paik CH, Old eld EH: Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with single-photon emission computerized tomography imaging. J Neurosurg 87: 586–594, 1997

    CAS  PubMed  Google Scholar 

  16. Weaver M, Laske DW: Transferrin receptor ligand-targeted toxin conjugate (Tf-CRM107)for therapy of malignant gliomas. J Neurooncol 65: 3–13, 2003

    PubMed  Google Scholar 

  17. Hall WA, Rustamzadeh E, Asher AL: Convection enhanced delivery in clinical trials. Neurosurg Focus 14: 2, 2003

    Google Scholar 

  18. Debinski W, Obiri NI, Pastan I, Puri RK: A novel chimeric protein composed of interleukin 13 and Pseudo-monas exotoxin is highly cytotoxic to human carcinoma cells expressing receptors for interleukin 13 and interleukin 4. J Biol Chem 270: 16775–16780, 1995

    CAS  PubMed  Google Scholar 

  19. 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 1: 1253–1258, 1995

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  21. Kunwar S: Convection enhanced delivery of IL13-PE38QQR for treatment of recurrent malignant glioma: presentation of interim findings from ongoing phase 1 studies. Acta Neurochir Suppl 88: 105–111, 2003

    CAS  PubMed  Google Scholar 

  22. Liu TF, Cohen 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 63: 1834–1837, 2003

    CAS  PubMed  Google Scholar 

  23. Liu TF, Cohen KA, Willingham MC, Tatter SB, Puri RK, Frankel AE: Combination fusion protein therapy of refractory brain tumors: demonstration of efficacy in cell culture. J Neurooncol 65: 77–85, 2003

    PubMed  Google Scholar 

  24. Barth S: hIL-13-PE38QQR. NeoPharm. Curr Opin Inves-tig Drugs 2: 1309–1313, 2001

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  26. Merlo A, Hausmann O, Wasner M, Steiner P, Otte A, Jermann E, Freitag P, Reubi JC, Muller-Brand J, Gratzl O, Macke HR: Locoregional regulatory peptide receptor targeting with the diffiusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas. Clin Cancer Res 5: 1025–1033, 1999

    CAS  PubMed  Google Scholar 

  27. Merlo A, Jermann E, Hausmann O, Chiquet-Ehrismann R, Probst A, Landolt H, Maecke HR, Mueller-Brand J, Gratzl O: Biodistribution of 111In-labelled SCN-bz-DTPA-BC-2 MAb following loco-regional injection into glioblastomas. Int J Cancer 71: 810–816, 1997

    CAS  PubMed  Google Scholar 

  28. Papanastassiou V, Pizer BL, Coakham HB, Bullimore J, Zananiri T, Kemshead JT: Treatment of recurrent and cystic malignant gliomas by a single intracavity injection of 131I monoclonal antibody: feasibility, pharmacokinetics and dosimetry. Br J Cancer 67: 144–151, 1993

    CAS  PubMed  Google Scholar 

  29. Riva P, Arista A, Franceschi G, Frattarelli M, Sturiale C, Riva N, Casi M, Rossitti R: Local treatment of malignant gliomas by direct infusion of specific monoclonal antibodies labeled with 131I: comparison of the results obtained in recurrent and newly diagnosed tumors. Cancer Res 55: 5952s–5956s, 1995

    CAS  PubMed  Google Scholar 

  30. Rainov NG: A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther 11: 2389–2401, 2000

    CAS  PubMed  Google Scholar 

  31. Chen Y, DeWeese T, Dilley J, Zhang Y, Li Y, Ramesh N, Lee J, Pennathur-Das R, Radzyminski J, Wypych J, Brignetti D, Scott S, Stephens J, Karpf DB, Henderson DR, Yu DC: CV706, a prostate cancer-specific adenovirus variant, in combination with radiotherapy produces synergistic antitumor efficacy without increasing toxicity. Cancer Res 61: 5453–5460, 2001

    CAS  PubMed  Google Scholar 

  32. Klatzmann D, Valery CA, Bensimon G, Marro B, Boyer O, Mokhtari K, Diquet B, Salzmann JL, Philippon J: A phase I/II study of herpes simplex virus type 1 thymidine kinase ‘suicide’ gene therapy for recurrent glioblastoma. Study Group on Gene Therapy for Glioblastoma. Hum Gene Ther 9: 2595–2604, 1998

    CAS  PubMed  Google Scholar 

  33. Puumalainen AM, Vapalahti M, Agrawal RS, Kossila M, Laukkanen J, Lehtolainen P, Viita H, Paljarvi L, Vanninen R, Yla-Herttuala S: Beta-galactosidase gene transfer to human malignant glioma in vivo using replication-deficient retroviruses and adenoviruses. Hum Gene Ther 9: 1769–1774, 1998

    CAS  PubMed  Google Scholar 

  34. Palu G, Cavaggioni A, Calvi P, Franchin E, Pizzato M, Boschetto R, Parolin C, Chilosi M, Ferrini S, Zanusso A, Colombo F: Gene therapy of glioblastoma multiforme via combined expression of suicide and cytokine genes: a pilot study in humans. Gene Ther 6: 330–337, 1999

    CAS  PubMed  Google Scholar 

  35. Trask TW, Trask RP, Aguilar-Cordova E, Shine HD, Wyde PR, Goodman JC, Hamilton WJ, Rojas-Martinez A, Chen SH, Woo SL, Grossman RG: Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. Mol Ther 1: 195–203, 2000

    CAS  PubMed  Google Scholar 

  36. Harsh GR, Deisboeck TS, Louis DN, Hilton J, Colvin M, Silver JS, Qureshi NH, Kracher J, Finkelstein D, Chiocca EA, Hochberg FH: Thymidine kinase activation of ganciclovir in recurrent malignant gliomas: a gene-marking and neuropathological study. J Neurosurg 92: 804–811, 2000

    CAS  PubMed  Google Scholar 

  37. Shand N, Weber F, Mariani L, Bernstein M, Gianella-Borradori A, Long Z, Sorensen AG, Barbier N: A phase 1–2 clinical trial of gene therapy for recurrent glioblastoma multiforme by tumor transduction with the herpes simplex thymidine kinase gene followed by ganciclovir. GLI328 European-Canadian Study Group. Hum Gene Ther 10: 2325–2335, 1999

    CAS  PubMed  Google Scholar 

  38. Lang FF, Bruner JM, Fuller GN, Aldape K, Prados MD, Chang S, Berger MS, McDermott MW, Kunwar SM, Junck LR, Chandler W, Zwiebel JA, Kaplan RS, Yung WK: Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J Clin Oncol 21: 2508–2518, 2003

    CAS  PubMed  Google Scholar 

  39. Rampling R, Cruickshank G, Papanastassiou V, Nicoll J, Hadley D, Brennan D, Petty R, MacLean A, Harland J, McKie E, Mabbs R, Brown M: Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716)in patients with recurrent malignant glioma. Gene Ther 7: 859–866, 2000

    CAS  PubMed  Google Scholar 

  40. Markert JM, Gillespie GY, Weichselbaum RR, Roizman B, Whitley RJ: Genetically engineered HSV in the treatment of glioma: a review. Rev Med Virol 10: 17–30, 2000

    CAS  PubMed  Google Scholar 

  41. Valery CA, Seilhean D, Boyer O, Marro B, Hauw JJ, Kemeny JL, Marsault C, Philippon J, Klatzmann D: Long-term survival after gene therapy for a recurrent glioblastoma. Neurology 58: 1109–1112, 2002

    CAS  PubMed  Google Scholar 

  42. Jacobs A, Voges J, Reszka R, Lercher M, Gossmann A, Kracht L, Kaestle C, Wagner R, Wienhard K, Heiss WD: Positron-emission tomography of vector-mediated gene expression in gene therapy for gliomas. Lancet 358: 727–729, 2001

    CAS  PubMed  Google Scholar 

  43. Voges J, Reszka R, Gossmann A, Dittmar C, Richter R, Garlip G, Kracht L, Coenen HH, Sturm V, Wienhard K, Heiss WD, Jacobs AH: Imaging-guided convection-enhanced delivery and gene therapy of glioblastoma. Ann Neurol 54: 479–487, 2003

    CAS  PubMed  Google Scholar 

  44. Moolten FL: Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res 46: 5276–5281, 1986

    CAS  PubMed  Google Scholar 

  45. Ram Z, Culver KW, Oshiro EM, Viola JJ, DeVroom HL, Otto E, Long Z, Chiang Y, McGarrity GJ, Muul LM, Katz D, Blaese RM, Oldfield EH: Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells. Nat Med 3: 1354–1361, 1997

    CAS  PubMed  Google Scholar 

  46. Prados M, Berger M: A phase II trial of gene therapy using an Ommaya reservoir to instill TK-retrovirus producer cells. J Neurooncology, in press

  47. Izquierdo M, Martin V, de Felipe P, Izquierdo JM, Perez-Higueras A, Cortes ML, Paz JF, Isla A, Blazquez MG: Human malignant brain tumor response to herpes simplex thymidine kinase (HSVtk)/ganciclovir gene therapy. Gene Ther 3: 491–495, 1996

    CAS  PubMed  Google Scholar 

  48. Sandmair AM, Loimas S, Puranen P, Immonen A, Kossila M, Puranen M, Hurskainen H, Tyynela K, Turunen M, Vanninen R, Lehtolainen P, Paljarvi L, Johansson R, Vapalahti M, Yla-Herttuala S: Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. Hum Gene Ther 11: 2197–2205, 2000

    CAS  PubMed  Google Scholar 

  49. Puumalainen AM, Vapalahti M, Yla-Herttuala S: Gene therapy for malignant glioma patients. Adv Exp Med Biol 451: 505–509, 1998

    CAS  PubMed  Google Scholar 

  50. Packer RJ, Raffiel C, Villablanca JG, Tonn JC, Burdach SE, Burger K, LaFond D, McComb JG, Cogen PH, Vezina G, Kapcala LP: Treatment of progressive or recurrent pediatric malignant supratentorial brain tumors with herpes simplex virus thymidine kinase gene vector-producer cells followed by intravenous ganciclovir administration. J Neurosurg 92: 249–254, 2000

    CAS  PubMed  Google Scholar 

  51. Markert JM, Medlock MD, Rabkin SD, Gillespie GY, Todo T, Hunter WD, Palmer CA, Feigenbaum F, Tornatore C, Tufaro F, Martuza RL: Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther 7: 867–874, 2000

    CAS  PubMed  Google Scholar 

  52. Floeth FW, Shand N, Bojar H, Prisack HB, Felsberg J, Neuen-Jacob E, Aulich A, Burger KJ, Bock WJ, Weber F: Local inffiammation and devascularization-in vivo mechanisms of the ‘bystander effect’ in VPC-mediated HSV-Tk/GCV gene therapy for human malignant glioma. Cancer Gene Ther 8: 843–851, 2001

    CAS  PubMed  Google Scholar 

  53. Smitt PS, Driesse M, Wolbers J, Kros M, Avezaat C: Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir. Mol Ther 7: 851–858, 2003

    CAS  PubMed  Google Scholar 

  54. Antonio Chiocca E: Oncolytic viruses. Nat Rev Cancer 2: 938–950, 2002

    CAS  PubMed  Google Scholar 

  55. Bischoffi JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, Nye JA, Sampson-Johannes A, Fattaey A, McCormick F: An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274: 373–376, 1996

    PubMed  Google Scholar 

  56. Boviatsis EJ, Park JS, Sena-Esteves M, Kramm CM, Chase M, Efird JT, Wei MX, Breakefield XO, Chiocca EA: Long-term survival of rats harboring brain neoplasms treated with ganciclovir and a herpes simplex virus vector that retains an intact thymidine kinase gene. Cancer Res 54: 5745–5751, 1994

    CAS  PubMed  Google Scholar 

  57. Fueyo J, Gomez-Manzano C, Alemany R, Lee PS, McDonnell TJ, Mitlianga P, Shi YX, Levin VA, Yung WK, Kyritsis AP: A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 19: 2–12, 2000

    CAS  PubMed  Google Scholar 

  58. Fulci G, Chiocca EA: Oncolytic viruses for the therapy of brain tumors and other solid malignancies: a review. Front Biosci 8: e346–e360, 2003

    CAS  PubMed  Google Scholar 

  59. Gromeier M, Wimmer E: Viruses for the treatment of malignant glioma. Curr Opin Mol Ther 3: 503–508, 2001

    CAS  PubMed  Google Scholar 

  60. Martuza RL, Malick A, Markert JM, Ruffiner KL, Coen DM: Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 252: 854–856, 1991

    CAS  PubMed  Google Scholar 

  61. Zhang JF, Hu C, Geng Y, Selm J, Klein SB, Orazi A, Taylor MW: Treatment of a human breast cancer xenograft with an adenovirus vector containing an interferon gene results in rapid regression due to viral oncolysis and gene therapy. Proc Natl Acad Sci USA 93: 4513–4518, 1996

    CAS  PubMed  Google Scholar 

  62. Yang WQ, Senger D, Muzik H, Shi ZQ, Johnson D, Brasher PM, Rewcastle NB, Hamilton M, Rutka J, Wolffi J, Wetmore C, Curran T, Lee PW, Forsyth PA: Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma. Cancer Res 63: 3162–3172, 2003

    CAS  PubMed  Google Scholar 

  63. Wilcox ME, Yang W, Senger D, Rewcastle NB, Morris DG, Brasher PM, Shi ZQ, Johnston RN, Nishikawa S, Lee PW, Forsyth PA: Reovirus as an oncolytic agent against experimental human malignant gliomas. J Natl Cancer Inst 93: 903–912, 2001

    CAS  PubMed  Google Scholar 

  64. Coffey MC, Strong JE, Forsyth PA, Lee PW: Reovirus therapy of tumors with activated Ras pathway. Science 282: 1332–1334, 1998

    CAS  PubMed  Google Scholar 

  65. Papanastassiou V, Rampling R, Fraser M, Petty R, Hadley D, Nicoll J, Harland J, Mabbs R, Brown M: The potential for efficacy of the modified (ICP 34. 5(-)) herpes simplex virus HSV1716 following intratumoural injection into human malignant glioma: a proof of principle study. Gene Ther 9: 398–406, 2002

    CAS  PubMed  Google Scholar 

  66. MacKie RM, Stewart B, Brown SM: Intralesional injection of herpes simplex virus 1716 in metastatic melanoma. Lancet 357: 525–526, 2001

    CAS  PubMed  Google Scholar 

  67. Mohr I, Gluzman Y: A herpesvirus genetic element which affects translation in the absence of the viral GADD34 function. Embo J 15: 4759–4766, 1996

    CAS  PubMed  Google Scholar 

  68. Philipson L, Pettersson U, Lindberg U: Molecular biology of adenoviruses. Virol Monogr 14: 1–115, 1975

    CAS  PubMed  Google Scholar 

  69. Marechal V, Piolot T: Lytic infection by double-strand DNA viruses and cell cycle alterations. Pathol Biol (Paris) 48: 289–300, 2000

    Google Scholar 

  70. Nemerow GR: Cell receptors involved in adenovirus entry. Virology 274: 1–4, 2000

    CAS  PubMed  Google Scholar 

  71. Hall AR, Dix BR, O’Carroll SJ, Braithwaite AW: p53-dependent cell death/apoptosis is required for a productive adenovirus infection. Nat Med 4: 1068–1072, 1998

    CAS  PubMed  Google Scholar 

  72. Goodrum FD, Ornelles DA: p53 status does not determine outcome of E1B 55-kilodalton mutant adenovirus lytic infection. J Virol 72: 9479–9490, 1998

    CAS  PubMed  Google Scholar 

  73. Heise CC, Williams AM, Xue S, Propst M, Kirn DH: Intravenous administration of ONYX-015, a selectively replicating adenovirus, induces antitumoral efficacy. Cancer Res 59: 2623–2628, 1999

    CAS  PubMed  Google Scholar 

  74. Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoffi DD, Kirn DH: ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med 3: 639–645, 1997

    CAS  PubMed  Google Scholar 

  75. Geoerger B, Grill J, Opolon P, Morizet J, Aubert G, Terrier-Lacombe MJ, Bressac De-Paillerets B, Barrois M, Feunteun J, Kirn DH, Vassal G: Oncolytic activity of the E1B-55 kDa-deleted adenovirus ONYX-015 is independent of cellular p53 status in human malignant glioma xenografts. Cancer Res 62: 764–772, 2002

    CAS  PubMed  Google Scholar 

  76. Post LE: Selectively replicating adenoviruses for cancer therapy: an update on clinical development. Curr Opin Investig Drugs 3: 1768–1772, 2002

    CAS  PubMed  Google Scholar 

  77. Reid T, Warren R, Kirn D: Intravascular adenoviral agents in cancer patients: lessons from clinical trials. Cancer Gene Ther 9: 979–986, 2002

    CAS  PubMed  Google Scholar 

  78. Kirn D: Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned?Gene Ther 8: 89–98, 2001

    CAS  PubMed  Google Scholar 

  79. Khuri FR, Nemunaitis J, Ganly I, Arseneau J, Tannock IF, Romel L, Gore M, Ironside J, MacDougall RH, Heise C, Randlev B, Gillenwater AM, Bruso P, Kaye SB, Hong WK, Kirn DH: A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med 6: 879–885, 2000

    CAS  PubMed  Google Scholar 

  80. Grill J, Van Beusechem VW, Van Der Valk P, Dirven CM, Leonhart A, Pherai DS, Haisma HJ, Pinedo HM, Curiel DT, Gerritsen WR: Combined targeting of adenoviruses to integrins and epidermal growth factor receptors increases gene transfer into primary glioma cells and spheroids. Clin Cancer Res 7: 641–650, 2001

    CAS  PubMed  Google Scholar 

  81. Lamfers ML, Grill J, Dirven CM, Van Beusechem VW, Geoerger B, Van Den Berg J, Alemany R, Fueyo J, Curiel DT, Vassal G, Pinedo HM, Vandertop WP, Gerritsen WR: Potential of the conditionally replicative adenovirus Ad5-Delta24RGD in the treatment of malignant gliomas and its enhanced effect with radiotherapy. Cancer Res 62: 5736–5742, 2002

    CAS  PubMed  Google Scholar 

  82. Miller CR, Buchsbaum DJ, Reynolds PN, Douglas JT, Gillespie GY, Mayo MS, Raben D, Curiel DT: Diffierential susceptibility of primary and established human glioma cells to adenovirus infection: targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer. Cancer Res 58: 5738–5748, 1998

    CAS  PubMed  Google Scholar 

  83. Fuxe J, Liu L, Malin S, Philipson L, Collins VP, Pettersson RF: Expression of the coxsackie and adenovirus receptor in human astrocytic tumors and xenografts. Int J Cancer 103: 723–729, 2003

    CAS  PubMed  Google Scholar 

  84. van Beusechem VWMDC, van den Doel P, Lamfers MLM, Grill J, Würdinger T, Haisma H, Pinedo HM, Gerritsen WR: Conditionally replicative adenovirus expressing a targeting adapter molecule exhibits enhanced oncolytic potency on CAR-deficient tumors. Gene Therapy, in press

  85. Staba MJ, Wickham TJ, Kovesdi I, Hallahan DE: Modifications of the fiber in adenovirus vectors increase tropism for malignant glioma models. Cancer Gene Ther 7: 13–19, 2000

    CAS  PubMed  Google Scholar 

  86. Dmitriev I, Krasnykh V, Miller CR, Wang M, Kashentseva E, Mikheeva G, Belousova N, Curiel DT: An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J Virol 72: 9706–9713, 1998

    CAS  PubMed  Google Scholar 

  87. Fueyo J, Alemany R, Gomez-Manzano C, Fuller GN, Khan A, Conrad CA, Liu TJ, Jiang H, Lemoine MG, Suzuki K, Sawaya R, Curiel DT, Yung WK, Lang FF: Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway. J Natl Cancer Inst 95: 652–660, 2003

    CAS  PubMed  Google Scholar 

  88. Shinoura N, Yoshida Y, Tsunoda R, Ohashi M, Zhang W, Asai A, Kirino T, Hamada H: Highly augmented cytopathic effect of a fiber-mutant E1B-defective adenovirus for gene therapy of gliomas. Cancer Res 59: 3411–3416, 1999

    CAS  PubMed  Google Scholar 

  89. Gu DL, Gonzalez AM, Printz MA, Doukas J, Ying W, D’Andrea M, Hoganson DK, Curiel DT, Douglas JT, Sosnowski BA, Baird A, Aukerman SL, Pierce GF: Fibroblast growth factor 2 retargeted adenovirus has redirected cellular tropism: evidence for reduced toxicity and enhanced antitumor activity in mice. Cancer Res 59: 2608–2614, 1999

    CAS  PubMed  Google Scholar 

  90. Douglas JT, Rogers BE, Rosenfeld ME, Michael SI, Feng M, Curiel DT: Targeted gene delivery by tropism-modified adenoviral vectors. Nat Biotechnol 14: 1574–1578, 1996

    CAS  PubMed  Google Scholar 

  91. Xia H, Anderson B, Mao Q, Davidson BL: Recombinant human adenovirus: targeting to the human transferring receptor improves gene transfer to brain microcapillary endothelium. J Virol 74: 11359–11336, 2000

    CAS  PubMed  Google Scholar 

  92. Fisher KD, Stallwood Y, Green NK, Ulbrich K, Mautner V, Seymour LW: Polymer-coated adenovirus permits efficient retargeting and evades neutralising antibodies. Gene Ther 8: 341–348, 2001

    CAS  PubMed  Google Scholar 

  93. Chen ZJ, Broaddus WC, Viswanathan RR, Raghavan R, Gillies GT: Intraparenchymal drug delivery via positive-pressure infusion: experimental and modeling studies of poroelasticity in brain phantom gels. IEEE Trans Biomed Eng 49: 85–96, 2002

    PubMed  Google Scholar 

  94. Chen MY, Lonser RR, Morrison PF, Governale LS, Oldfield EH: Variables affecting convection-enhanced delivery to the striatum: a systematic examination of rate of infusion, cannula size, infusate concentration, and tissue-cannula sealing time. J Neurosurg 90: 315–320, 1999

    CAS  PubMed  Google Scholar 

  95. Freeman TB, Hauser RA, Sanberg PR: Fatal transplant cyst. J Neurosurg 90: 1148–1150, 1999

    CAS  Google Scholar 

  96. Gillies GT and Allison SW: Positive pressure infusion of fluorescent nanoparticles as a probe of the structure of brain phantom gelatins. Nanotechnol 13: 484–486, 2002

    CAS  Google Scholar 

  97. Gillies GT, Kucharczyk J, Broaddus WC: MR-visible medical device for neurological interventions using non-linear magnetic stereotaxis and a method of imaging. US Patent No. 6,272,370: August 7, 2001

  98. Kucharczyk J, Gillies GT: Multi-Probe System. US Patent No. 6,626,902: September 30, 2003

  99. Kucharczyk J, Broaddus WC, Fillmore HL: Cell delivery catheter and method. US Patent No. 6,599,274: July 29, 2003

  100. Bauman MA, Gillies GT, Raghavan R: Physical characterization of neurocatheter performance in a brain phantom gelatin with nanoscale porosity: stead-state and oscillatoryffiows. Nanotechnol 15: 92–97, 2004

    CAS  Google Scholar 

  101. Prabhu SS, Broaddus WC, Oveissi C, Berr SS, Gillies GT: Determination of intracranial tumor volumes in a rodent brain using magnetic resonance imaging, Evans blue, and histology: a comparative study. IEEE Trans Biomed Eng 47: 259–265, 2000

    CAS  PubMed  Google Scholar 

  102. Grady MS, Howard MA, 3rd, Dacey RG, Jr, Blume W, Lawson M, Werp P, Ritter RC: Experimental study of the magnetic stereotaxis system for catheter manipulation within the brain. J Neurosurg 93: 282–288, 2000

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. E. Antonio Chiocca

    Present address: Molecular Neuro-Oncology Laboratories, Neurosurgery Service, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA

Authors and Affiliations

  1. Department of Neurosurgery, Medical College of Virginia Hospitals, Virginia Commonwealth University, Richmond, USA

    William C. Broaddus

  2. Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA

    George T. Gillies

Authors
  1. E. Antonio Chiocca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William C. Broaddus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George T. Gillies
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Therese Visted
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martine L.M. Lamfers
    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

Chiocca, E.A., Broaddus, W.C., Gillies, G.T. et al. Neurosurgical Delivery of Chemotherapeutics, Targeted Toxins, Genetic and Viral Therapies in Neuro-Oncology. J Neurooncol 69, 101–117 (2004). https://doi.org/10.1023/B:NEON.0000041874.02554.b3

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NEON.0000041874.02554.b3

Search

Navigation