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.
Similar content being viewed by others
References
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
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
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
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
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
Chiocca EA: Gene therapy: a primer for neurosurgeons. Neurosurgery 53: 364–373;discussion 373, 2003
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
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
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
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
Pietronigro D, Drnovsky F, Cravioto H, Ransohoffi J: DTI-015 produces cures in T9 gliosarcoma. Neoplasia 5: 17–22, 2003
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
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
Hall WA: Immunotoxin treatment of brain tumors. Methods Mol Biol 166: 139–154, 2001
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
Weaver M, Laske DW: Transferrin receptor ligand-targeted toxin conjugate (Tf-CRM107)for therapy of malignant gliomas. J Neurooncol 65: 3–13, 2003
Hall WA, Rustamzadeh E, Asher AL: Convection enhanced delivery in clinical trials. Neurosurg Focus 14: 2, 2003
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
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
Husain SR, Puri RK: Interleukin-13 receptor-directed cytotoxin for malignant glioma therapy: from bench to bedside. J Neurooncol 65: 37–48, 2003
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
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
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
Barth S: hIL-13-PE38QQR. NeoPharm. Curr Opin Inves-tig Drugs 2: 1309–1313, 2001
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Moolten FL: Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res 46: 5276–5281, 1986
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
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
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
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
Puumalainen AM, Vapalahti M, Yla-Herttuala S: Gene therapy for malignant glioma patients. Adv Exp Med Biol 451: 505–509, 1998
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
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
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
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
Antonio Chiocca E: Oncolytic viruses. Nat Rev Cancer 2: 938–950, 2002
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
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
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
Fulci G, Chiocca EA: Oncolytic viruses for the therapy of brain tumors and other solid malignancies: a review. Front Biosci 8: e346–e360, 2003
Gromeier M, Wimmer E: Viruses for the treatment of malignant glioma. Curr Opin Mol Ther 3: 503–508, 2001
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
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
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
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
Coffey MC, Strong JE, Forsyth PA, Lee PW: Reovirus therapy of tumors with activated Ras pathway. Science 282: 1332–1334, 1998
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
MacKie RM, Stewart B, Brown SM: Intralesional injection of herpes simplex virus 1716 in metastatic melanoma. Lancet 357: 525–526, 2001
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
Philipson L, Pettersson U, Lindberg U: Molecular biology of adenoviruses. Virol Monogr 14: 1–115, 1975
Marechal V, Piolot T: Lytic infection by double-strand DNA viruses and cell cycle alterations. Pathol Biol (Paris) 48: 289–300, 2000
Nemerow GR: Cell receptors involved in adenovirus entry. Virology 274: 1–4, 2000
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
Goodrum FD, Ornelles DA: p53 status does not determine outcome of E1B 55-kilodalton mutant adenovirus lytic infection. J Virol 72: 9479–9490, 1998
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
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
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
Post LE: Selectively replicating adenoviruses for cancer therapy: an update on clinical development. Curr Opin Investig Drugs 3: 1768–1772, 2002
Reid T, Warren R, Kirn D: Intravascular adenoviral agents in cancer patients: lessons from clinical trials. Cancer Gene Ther 9: 979–986, 2002
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Freeman TB, Hauser RA, Sanberg PR: Fatal transplant cyst. J Neurosurg 90: 1148–1150, 1999
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
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
Kucharczyk J, Gillies GT: Multi-Probe System. US Patent No. 6,626,902: September 30, 2003
Kucharczyk J, Broaddus WC, Fillmore HL: Cell delivery catheter and method. US Patent No. 6,599,274: July 29, 2003
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
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
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
Author information
Authors and Affiliations
Rights 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
Issue Date:
DOI: https://doi.org/10.1023/B:NEON.0000041874.02554.b3