恶性胶质瘤溶瘤病毒治疗进展

doi:10.3969/j.issn.1672-6731.2020.02.007

摘要/Abstract

摘要：

恶性胶质瘤是侵袭性最强的原发性脑肿瘤，预后极差，治疗后中位生存期仅14.6个月，因此迫切需要探寻针对胶质母细胞瘤的新的有效治疗方法。溶瘤病毒疗法属于免疫治疗，以病毒特异性感染肿瘤细胞并通过释放病毒后代进而诱导肿瘤细胞溶解为特点。目前临床前研究业已证实溶瘤病毒疗法的有效性和安全性，现将进入临床试验阶段的溶瘤病毒疗法进行综述。

关键词: 神经胶质瘤, 溶瘤病毒疗法, 综述

Abstract:

Malignant glioma is the most highly invasive primary brain tumor associated with an extremely poor prognosis and median survival of only 14.6 months. An improved treatment for glioblastoma is urgently needed. Unique to oncolytic viruses (OVs) is the ability of the virus to infect specifically a tumor cell and induce tumor lysis through the release of viral progeny, which can subsequently infect nearby tumor cells. Several OVs proved their safety and efficacy in several preclinical studies. In this review, we report the OVs that successfully transferred into the clinical trials.

Key words: Glioma, Oncolytic virotherapy, Review

刘鸿宇, 余新光, 陈凌. 恶性胶质瘤溶瘤病毒治疗进展[J]. 中国现代神经疾病杂志, 2020, 20(2): 111-118.

LIU Hong-yu, YU Xin-guang, CHEN Ling. Oncolytic viruses for the treatment of malignant glioma[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2020, 20(2): 111-118.

http://journal11.magtechjournal.com/cjcnn/CN/Y2020/V20/I2/111

参考文献

[1] Parker JN, Bauer DF, Cody JJ, Markert JM. Oncolytic viral therapy of malignant glioma[J]. Neurotherapeutics, 2009, 6:558-569.
[2] Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma[J]. N Engl J Med, 2005, 352:987-996.
[3] Hulou MM, Cho CF, Chiocca EA, Bjerkvig R. Experimental therapies:gene therapies and oncolytic viruses[J]. Handb Clin Neurol, 2016, 134:183-197.
[4] Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response[J]. Nature, 2006, 444:756-760.
[5] Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells[J]. Nature, 2004, 432:396-401.
[6] Kaufmann JK, Chiocca EA. Glioma virus therapies between bench and bedside[J]. Neuro Oncol, 2014, 16:334-351.
[7] De Pace NG. Sulla scomparsa di un enorme cancro vegetante del callo dell'utero senza cura chirurgica[J]. Ginecologia (France), 1912, 9:82-88.
[8] Higgins GK, Pack GT. Virus therapy in the treatment of tumors[J]. Bull Hosp Joint Dis, 1951, 12:379-382.
[9] Pack GT. Note on the experimental use of rabies vaccine for melanomatosis[J]. AMA Arch Derm Syphilol, 1950, 62:694-695.
[10] Bluming AZ, Ziegler JL. Regression of Burkitt's lymphoma in association with measles infection[J]. Lancet, 1971, 2:105-106.
[11] Taqi AM, Abdurrahman MB, Yakubu AM, Fleming AF. Regression of Hodgkin's disease after measles[J]. Lancet, 1981, 1:1112.
[12] Martuza RL, Malick A, Markert JM, Ruffner KL, Coen DM. Experimental therapy of human glioma by means of a genetically engineered virus mutant[J]. Science, 1991, 252:854-856.
[13] 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[J]. Gene Ther, 2000, 7:867-874.
[14] 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[J]. Gene Ther, 2000, 7:859-866.
[15] 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[J]. Gene Ther, 2002, 9:398-406.
[16] Harrow S, Papanastassiou V, Harland J, Mabbs R, Petty R, Fraser M, Hadley D, Patterson J, Brown SM, Rampling R. HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma:safety data and long-term survival[J]. Gene Ther, 2004, 11:1648-1658.
[17] Markert JM, Liechty PG, Wang W, Gaston S, Braz E, Karrasch M, Nabors LB, Markiewicz M, Lakeman AD, Palmer CA, Parker JN, Whitley RJ, Gillespie GY. Phase Ⅰ b trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM[J]. Mol Ther, 2009, 17:199-207.
[18] Markert JM, Razdan SN, Kuo HC, Cantor A, Knoll A, Karrasch M, Nabors LB, Markiewicz M, Agee BS, Coleman JM, Lakeman AD, Palmer CA, Parker JN, Whitley RJ, Weichselbaum RR, Fiveash JB, Gillespie GY. A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses[J]. Mol Ther, 2014, 22:1048-1055.
[19] Todo T, Martuza RL, Rabkin SD, Johnson PA. Oncolytic herpes simplex virus vector with enhanced MHC class i presentation and tumor cell killing[J]. Proc Natl Acad Sci USA, 2001, 98:6396-6401.
[20] Whyte P, Williamson NM, Harlow E. Cellular targets for transformation by the adenovirus E1A proteins[J]. Cell, 1989, 56:67-75.
[21] Patel DM, Foreman PM, Nabors LB, Riley KO, Gillespie GY, Markert JM. Design of a phase Ⅰ clinical trial to evaluate M032, a genetically engineered HSV-1 expressing IL-12, in patients with recurrent/progressive glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma[J]. Hum Gene Ther Clin Dev, 2016, 27:69-78.
[22] Lang FF, Conrad C, Gomez-Manzano C, Yung WK, Sawaya R, Weinberg JS, Prabhu SS, Rao G, Fuller GN, Aldape KD, Gumin J, Vence LM, Wistuba I, Rodriguez-Canales J, Villalobos PA, Dirven CMF, Tejada S, Valle RD, Alonso MM, Ewald B, Peterkin JJ, Tufaro F, Fueyo J. Phase Ⅰ study of DNX-2401(Delta-24-RGD) oncolytic adenovirus:replication and immunotherapeutic effects in recurrent malignant glioma[J]. J Clin Oncol, 2018, 36:1419-1427.
[23] Lang FF, Conrad C, Gomez-Manzano C, Tufaro F, Yung W, Sawaye R. First-in-human phase Ⅰ clinical trial of oncolytic delta-24-rgd (dnx-2401) with biological endpoints:implications for viro-immunotherapy[J]. Neuro Oncol, 2014, 16(Suppl 3):iii39.
[24] Strong JE, Coffey MC, Tang D, Sabinin P, Lee PW. The molecular basis of viral oncolysis:usurpation of the Ras signaling pathway by reovirus[J]. EMBO J, 1998, 17:3351-3362.
[25] Kicielinski KP, Chiocca EA, Yu JS, Gill GM, Coffey M, Markert JM. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults[J]. Mol Ther, 2014, 22:1056-1062.
[26] Alexander DJ, Allan WH. Newcastle disease virus pathotypes[J]. Avian Pathol, 1974, 3:269-278.
[27] Geletneky K, Herrero Y, Calle M, Rommelaere J, Schlehofer JR. Oncolytic potential of rodent parvoviruses for cancer therapy in humans:a brief review[J]. J Vet Med B Infect Dis Vet Public Health, 2005, 52:327-330.
[28] Gromeier M, Alexander L, Wimmer E. Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants[J]. Proc Natl Acad Sci USA, 1996, 93:2370-2375.
[29] Martinez-Velez N, Marigil M, Garcia-Moure M, Gonzalez-Huarriz M, Aristu JJ, Ramos-García LI, Tejada S, Díez-Valle R, Patiño-García A, Becher OJ, Gomez-Manzano C, Fueyo J, Alonso MM. Delta-24-RGD combined with radiotherapy exerts a potent antitumor effect in diffuse intrinsic pontine glioma and pediatric high grade glioma models[J]. Acta Neuropathol Commun, 2019, 7:64.
[30] Wollmann G, Ozduman K, van den Pol AN. Oncolytic virus therapy for glioblastomamultiforme:concepts and candidates[J]. Cancer J, 2012, 18:69-81.
[31] He B, Gross M, Roizman B. The gamma (1)34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1alpha to dephosphorylate the alpha subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase[J]. Proc Natl Acad Sci USA, 1997, 94:843-848.
[32] Whitley RJ, Kern ER, Chatterjee S, Chou J, Roizman B. Replication, establishment of latency, and induced reactivation of herpes simplex virus gamma 134.5 deletion mutants in rodent models[J]. J Clin Invest, 1993, 91:2837-2843.
[33] Goldstein DJ, Weller SK. Factor (s) present in herpes simplex virus type 1-infected cells can compensate for the loss of the large subunit of the viral ribonucleotide reductase:characterization of an ICP6 deletion mutant[J]. Virology, 1988, 166:41-51.
[34] Coen DM, Goldstein DJ, Weller SK. Herpes simplex virus ribonucleotide reductase mutants are hypersensitive to acyclovir[J]. Antimicrob Agents Chemother, 1989, 33:1395-1399.
[35] Mineta T, Rabkin SD, Yazaki T, Hunter WD, Martuza RL. Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas[J]. Nat Med, 1995, 1:938-943.
[36] Hunter WD, Martuza RL, Feigenbaum F, Todo T, Mineta T, Yazaki T, Toda M, Newsome JT, Platenberg RC, Manz HJ, Rabkin SD. Attenuated, replication-competent herpes simplex virus type 1 mutant G207:safety evaluation of intracerebral injection in nonhuman primates[J]. J Virol, 1999, 73:6319-6326.
[37] Sundaresan P, Hunter WD, Martuza RL, Rabkin SD. Attenuated, replication-competent herpes simplex virus type 1 mutant G207:safety evaluation in mice[J]. J Virol, 2000, 74:3832-3841.
[38] Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy:a new era of cancer treatment at dawn[J]. Cancer Sci, 2016, 107:1373-1379.
[39] 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[J]. Oncogene, 2000, 19:2-12.
[40] Bischoff 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[J]. Science, 1996, 274:373-376.
[41] O'Shea CC, Johnson L, Bagus B, Choi S, Nicholas C, Shen A, Boyle L, Pandey K, Soria C, Kunich J, Shen Y, Habets G, Ginzinger D, McCormick F. Late viral RNA export, rather than p53 inactivation, determines ONYX-015 tumor selectivity[J]. Cancer Cell, 2004, 6:611-623.
[42] Chiocca EA, Abbed KM, Tatter S, Louis DN, Hochberg FH, Barker F, Kracher J, Grossman SA, Fisher JD, Carson K, Rosenblum M, Mikkelsen T, Olson J, Markert J, Rosenfeld S, Nabors LB, Brem S, Phuphanich S, Freeman S, Kaplan R, Zwiebel J. A phase Ⅰ open-label, dose-escalation, multi-institutional trial of injection with an E1B-Attenuated adenovirus, ONYX-015, into the peritumoral region of recurrent malignant gliomas, in the adjuvant setting[J]. Mol Ther, 2004, 10:958-966.
[43] Nishikawa R, Ji XD, Harmon RC, Lazar CS, Gill GN, Cavenee WK, Huang HJ. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity[J]. Proc Natl Acad Sci USA, 1994, 91:7727-7731.
[44] Gong J, Mita MM. Activated ras signaling pathways and reovirus oncolysis:an update on the mechanism of preferential reovirus replication in cancer cells[J]. Front Oncol, 2014, 4:167.
[45] Forsyth P, Roldan G, George D, Wallace C, Palmer CA, Morris D, Cairncross G, Matthews MV, Markert J, Gillespie Y, Coffey M, Thompson B, Hamilton M. A phase Ⅰ trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas[J]. Mol Ther, 2008, 16:627-632.
[46] Flanagan AD, Love R, Tesar W. Propagation of Newcastle disease virus in Ehrlich ascites cells in vitro and in vivo[J]. Proc Soc Exp Biol Med, 1955, 90:82-86.
[47] Lorence RM, Reichard KW, Katubig BB, Reyes HM, Phuangsab A, Mitchell BR, Cascino CJ, Walter RJ, Peeples ME. Complete regression of human neuroblastoma xenografts in athymicmice after local Newcastle disease virus therapy[J]. J Natl Cancer Inst, 1994, 86:1228-1233.
[48] Lorence RM, Katubig BB, Reichard KW, Reyes HM, Phuangsab A, Sassetti MD, Walter RJ, Peeples ME. Complete regression of human fibrosarcoma xenografts after local Newcastle disease virus therapy[J]. Cancer Res, 1994, 54:6017-6021.
[49] Csatary LK, Bakács T. Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma[J]. JAMA, 1999, 281:1588-1589.
[50] Csatary LK, Gosztonyi G, Szeberenyi J, Fabian Z, Liszka V, Bodey B, Csatary CM. MTH-68/H oncolytic viral treatment in human high-grade gliomas[J]. J Neurooncol, 2004, 67:83-93.
[51] Wagner S, Csatary CM, Gosztonyi G, Koch HC, Hartmann C, Peters O, Hernáiz-Driever P, Théallier-Janko A, Zintl F, Längler A, Wolff JE, Csatary LK. Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid[J]. APMIS, 2006, 114:731-743.
[52] Freeman AI, Zakay-Rones Z, Gomori JM, Linetsky E, Rasooly L, Greenbaum E, Rozenman-Yair S, Panet A, Libson E, Irving CS, Galun E, Siegal T. Phase Ⅰ/Ⅱ trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme[J]. Mol Ther, 2006, 13:221-228.
[53] Rommelaere J, Geletneky K, Angelova AL, Daeffler L, Dinsart C, Kiprianova I, Schlehofer JR, Raykov Z. Oncolytic parvoviruses as cancer therapeutics[J]. Cytokine Growth Factor Rev, 2010, 21:185-195.
[54] Rommelaere J, Cornelis JJ. Antineoplastic activity of parvoviruses[J]. J Virol Methods, 1991, 33:233-251.
[55] Herrero Y, Calle M, Cornelis JJ, Herold-Mende C, Rommelaere J, Schlehofer JR, Geletneky K. Parvovirus H-1 infection of human glioma cells leads to complete viral replication and efficient cell killing[J]. Int J Cancer, 2004, 109:76-84.
[56] Geletneky K, Kiprianova I, Ayache A, Koch R, Herrero Y, Calle M, Deleu L, Sommer C, Thomas N, Rommelaere J, Schlehofer JR. Regression of advanced rat and human gliomas by local or systemic treatment with oncolytic parvovirus H-1 in rat models[J]. Neuro Oncol, 2010, 12:804-814.
[57] Geletneky K, Hajda J, Angelova AL, Leuchs B, Capper D, Bartsch AJ, Neumann JO, Schöning T, Hüsing J, Beelte B, Kiprianova I, Roscher M, Bhat R, von Deimling A, Brück W, Just A, Frehtman V, Löbhard S, Terletskaia-Ladwig E, Fry J, Jochims K, Daniel V, Krebs O, Dahm M, Huber B, Unterberg A, Rommelaere J. Oncolytic H-1 parvovirus ahows safety and signs of immunogenic activity in a first phase Ⅰ/Ⅱ a glioblastoma trial[J]. Mol Ther, 2017, 25:2620-2634.
[58] Gromeier M, Lachmann S, Rosenfeld MR, Gutin PH, Wimmer E. Intergeneric poliovirus recombinants for the treatment of malignant glioma[J]. Proc Natl Acad Sci USA, 2000, 97:6803-6808.
[59] Merrill MK, Bernhardt G, Sampson JH, Wikstrand CJ, Bigner DD, Gromeier M. Poliovirus receptor CD155-targeted oncolysis of glioma[J]. Neuro Oncol, 2004, 6:208-217.
[60] Desjardins A, Gromeier M, Herndon JE 2nd, Beaubier N, Bolognesi DP, Friedman AH, Friedman HS, McSherry F, Muscat AM, Nair S, Peters KB, Randazzo D, Sampson JH, Vlahovic G, Harrison WT, McLendon RE, Ashley D, Bigner DD. Recurrent glioblastoma treated with recombinant poliovirus[J]. N Engl J Med, 2018, 379:150-161.
[61] Martínez-Vélez N, Garcia-Moure M, Marigil M, González-Huarriz M, Puigdelloses M, Gallego Pérez-Larraya J, Zalacaín M, Marrodán L, Varela-Guruceaga M, Laspidea V, Aristu JJ, Ramos LI, Tejada-Solís S, Díez-Valle R, Jones C, Mackay A, Martínez-Climent JA, García-Barchino MJ, Raabe E, Monje M, Becher OJ, Junier MP, El-Habr EA, Chneiweiss H, Aldave G, Jiang H, Fueyo J, Patiño-García A, Gomez-Manzano C, Alonso MM. The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models[J]. Nat Commun, 2019, 10:2235.
[62] Saha D, Martuza RL, Rabkin SD. Macrophage polarization contributes to glioblastoma eradication by combination immunovirotherapy and immune checkpoint blockade[J]. Cancer Cell, 2017, 32:253-267.
[63] Jiang H, Rivera-Molina Y, Gomez-Manzano C, Clise-Dwyer K, Bover L, Vence LM, Yuan Y, Lang FF, Toniatti C, Hossain MB, Fueyo J. Oncolytic adenovirus and tumor-targeting immune modulatory therapy improve autologous cancer vaccination[J]. Cancer Res, 2017, 77:3894-3907.
[64] Samson A, Scott KJ, Taggart D, West EJ, Wilson E, Nuovo GJ, Thomson S, Corns R, Mathew RK, Fuller MJ, Kottke TJ, Thompson JM, Ilett EJ, Cockle JV, van Hille P, Sivakumar G, Polson ES, Turnbull SJ, Appleton ES, Migneco G, Rose AS, Coffey MC, Beirne DA, Collinson FJ, Ralph C, Alan Anthoney D, Twelves CJ, Furness AJ, Quezada SA, Wurdak H, Errington-Mais F, Pandha H, Harrington KJ, Selby PJ, Vile RG, Griffin SD, Stead LF, Short SC, Melcher AA. Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade[J]. Sci Transl Med, 2018, 10:eaam7577.
[65] Hardcastle J, Mills L, Malo CS, Jin F, Kurokawa C, Geekiyanage H, Schroeder M, Sarkaria J, Johnson AJ, Galanis E. Immunovirotherapy with measles virus strains in combination with anti-PD-1 antibody blockade enhances antitumor activity in glioblastoma treatment[J]. Neuro Oncol, 2017, 19:493-502.

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