Pathogens and glioma: a history of unexpected discoveries ushering in novel therapy

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In the late 19th century, Dr. William B. Coley introduced the theory that infections may aid in the treatment of malignancy. With the creation of Coley’s toxin, reports of remission during viral illnesses for systemic malignancies soon emerged. A few decades after this initial discovery, Austrian physicians performed intravascular injections of Clostridium to induce oncolysis in patients with glioblastoma. Since then, suggestions between improved survival and infectious processes have been reported in several patients with glioma, which ultimately marshaled the infamous use of intracerebral Enterobacter. These early observations of tumor regression and concomitant infection piloted a burgeoning field focusing on the use of pathogens in molecular oncology.

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Contributor Notes

Correspondence Ashish H. Shah, Department of Neurological Surgery, University of Miami Miller School of Medicine, 1095 NW 14th Terrace, Rm. 2-06, Miami, FL 33136. email: ashah@med.miami.edu.INCLUDE WHEN CITING Published online June 9, 2017; DOI: 10.3171/2016.12.JNS162123.Disclosures Dr. Ivan has served as a consultant to Medtronic. Dr. Kasahara has served as a consultant to Tocagen Inc.

© AANS, except where prohibited by US copyright law.

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References
  • 1

    Asada T: Treatment of human cancer with mumps virus. Cancer 34:190719281974

  • 2

    Baker M: Can bacteria fight brain cancer? Nature News Explainer. July 27 2012. (http://www.nature.com/news/can-bacteria-fight-brain-cancer-1.11080) [Accessed February 21 2017]

    • Search Google Scholar
    • Export Citation
  • 3

    Bickels JKollender YMerinsky OMeller I: Coley’s toxin: historical perspective. Isr Med Assoc J 4:4714722002

  • 4

    Bierman HRCrile DMDod KSKelly KHPetrakis NLWhite LP: Remissions in leukemia of childhood following acute infectious disease: staphylococcus and streptococcus, varicella, and feline panleukopenia. Cancer 6:5916051953

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Bischoff JRKirn DHWilliams AHeise CHorn SMuna M: An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science 274:3733761996

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Bluming AZZiegler JL: Regression of Burkitt’s lymphoma in association with measles infection. Lancet 2:1051061971

  • 7

    Bohman LEGallardo JHankinson TCWaziri AEMandigo CEMcKhann GM II: The survival impact of postoperative infection in patients with glioblastoma multiforme. Neurosurgery 64:8288352009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Bowles AP JrPerkins E: Long-term remission of malignant brain tumors after intracranial infection: a report of four cases. Neurosurgery 44:6366431999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Broaddus WCLiu YSteele LLGillies GTLin PSLoudon WG: Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction. J Neurosurg 91:99710041999

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Coley WB: Contribution to the study of sarcoma of the femur. Ann Surg 58:971081913

  • 11

    Coley WB: The treatment of inoperable sarcoma by bacterial toxins (the mixed toxins of the Streptococcus erysipelas and the Bacillus prodigiosus). Proc R Soc Med 3 (Surg Sect):1481910

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Coley WB: The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res (262):3–111991

    • Search Google Scholar
    • Export Citation
  • 13

    Chen SHShine HDGoodman JCGrossman RGWoo SL: Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo. Proc Natl Acad Sci U S A 91:305430571994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Chiocca EAAbbed KMTatter SLouis DNHochberg FHBarker F: 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. Mol Ther 10:9589662004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Chiocca EAAguilar LKBell SDKaur BHardcastle JCavaliere R: Phase IB study of gene-mediated cytotoxic immunotherapy adjuvant to up-front surgery and intensive timing radiation for malignant glioma. J Clin Oncol 29:361136192011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Chiocca EASmith KMMcKinney BPalmer CARosenfeld SLillehei K: A phase I trial of Ad.hIFN-beta gene therapy for glioma. Mol Ther 16:6186262008

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    De Bonis PAlbanese ALofrese Gde Waure CMangiola APettorini BL: Postoperative infection may influence survival in patients with glioblastoma: simply a myth? Neurosurgery 69:8648692011

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    De Pace N: Sulla scomparsa di un enorme cancro vegetante del callo dell’utero senza cura chirurgica. Ginecologia (France) 9:82881912

    • Search Google Scholar
    • Export Citation
  • 19

    Dock G: The influence of complicating diseases upon leukemia. Am J Med Sci 127:5635921904

  • 20

    Forsyth PRoldán GGeorge DWallace CPalmer CAMorris D: A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas. Mol Ther 16:6276322008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Freeman AIZakay-Rones ZGomori JMLinetsky ERasooly LGreenbaum E: Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme. Mol Ther 13:2212282006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Geletneky KHuesing JRommelaere JSchlehofer JRLeuchs BDahm M: Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol. BMC Cancer 12:992012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Germano IMFable JGultekin SHSilvers A: Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: preliminary results of a phase I trial in patients with recurrent malignant gliomas. J Neurooncol 65:2792892003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Goetz CDobrikova EShveygert MDobrikov MGromeier M: Oncolytic poliovirus against malignant glioma. Future Virol 6:104510582011

  • 25

    Harrow SPapanastassiou VHarland JMabbs RPetty RFraser M: HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival. Gene Ther 11:164816582004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Heise CSampson-Johannes AWilliams AMcCormick FVon Hoff DDKirn 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 3:6396451997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Heppner FMöse JR: The liquefaction (oncolysis) of malignant gliomas by a non pathogenic Clostridium. Acta Neurochir (Wien) 42:1231251978

  • 28

    Horowitz J: Adenovirus-mediated p53 gene therapy: overview of preclinical studies and potential clinical applications. Curr Opin Mol Ther 1:5005091999

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Huebner RJRowe WPSchatten WESmith RRThomas LB: Studies on the use of viruses in the treatment of carcinoma of the cervix. Cancer 9:121112181956

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Immonen AVapalahti MTyynelä KHurskainen HSandmair AVanninen R: AdvHSV-tk gene therapy with intravenous ganciclovir improves survival in human malignant glioma: a randomised, controlled study. Mol Ther 10:9679722004

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Ji NWeng DLiu CGu ZChen SGuo Y: Adenovirus-mediated delivery of herpes simplex virus thymidine kinase administration improves outcome of recurrent high-grade glioma. Oncotarget 7:436943782016

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Jiang HClise-Dwyer KRuisaard KEFan XTian WGumin J: Delta-24-RGD oncolytic adenovirus elicits anti-glioma immunity in an immunocompetent mouse model. PLoS One 9:e974072014

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33

    Jiang HGomez-Manzano CAoki HAlonso MMKondo SMcCormick F: Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death. J Natl Cancer Inst 99:141014142007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Kapp JP: Microorganisms as antineoplastic agents in CNS tumors. Arch Neurol 40:6376421983

  • 35

    Kicielinski KPChiocca EAYu JSGill GMCoffey MMarkert JM: Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther 22:105610622014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    King GDMuhammad AKLarocque DKelson KRXiong WLiu C: Combined Flt3L/TK gene therapy induces immunological surveillance which mediates an immune response against a surrogate brain tumor neoantigen. Mol Ther 19:179318012011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Lang FFBruner JMFuller GNAldape KPrados MDChang S: Phase I trial of adenovirus-mediated p53 gene therapy for recurrent glioma: biological and clinical results. J Clin Oncol 21:250825182003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Lang FFConrad CGomez-Manzano CTufaro FYung WKASawaya R: First-in-human Phase I clinical trial of oncolytic Delta-24-Rgd (Dnx-2401) with biological endpoints: implications for viro-immunotherapy. Neuro Oncol 16 (Suppl 3):iii39 2014 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 39

    Li HAlonso-Vanegas MColicos MAJung SSLochmuller HSadikot AF: Intracerebral adenovirus-mediated p53 tumor suppressor gene therapy for experimental human glioma. Clin Cancer Res 5:6376421999

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Markert JMLiechty PGWang WGaston SBraz EKarrasch M: Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM. Mol Ther 17:1992072009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Markert JMMedlock MDRabkin SDGillespie GYTodo THunter WD: Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther 7:8678742000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Marth EAscher WPPavelka RMöse JR: Tumor lysis of a glioblastoma by Clostridium oncolyticum. J Chemother 1 (4 Suppl):117711781989

  • 43

    Martuza RLMalick AMarkert JMRuffner KLCoen DM: Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 252:8548561991

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44

    Moese JRMoese G: Oncolysis by Clostridia. I. Activity of Clostridium butyricum (M-55) and other nonpathogenic Clostridia against the Ehrlich carcinoma. Cancer Res 24:2122161964

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Moolten FLWells JM: Curability of tumors bearing herpes thymidine kinase genes transferred by retroviral vectors. J Natl Cancer Inst 82:2973001990

  • 46

    Myers RHarvey MKaufmann TJGreiner SMKrempski JWRaffel C: Toxicology study of repeat intracerebral administration of a measles virus derivative producing carcinoembryonic antigen in rhesus macaques in support of a phase I/II clinical trial for patients with recurrent gliomas. Hum Gene Ther 19:6906982008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Nanda DVogels RHavenga MAvezaat CJBout ASmitt PS: Treatment of malignant gliomas with a replicating adenoviral vector expressing herpes simplex virus-thymidine kinase. Cancer Res 61:874387502001

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48

    Nauts HCSwift WEColey BL: The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, M.D., reviewed in the light of modern research. Cancer Res 6:2052161946

    • Search Google Scholar
    • Export Citation
  • 49

    Okuno YAsada TYamanishi KOtsuka TTakahashi MTanioka T: Studies on the use of mumps virus for treatment of human cancer. Biken J 21:37491978

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 50

    Pan DWei XLiu MFeng STian XFeng X: Adenovirus mediated transfer of p53, GM-CSF and B7-1 suppresses growth and enhances immunogenicity of glioma cells. Neurol Res 32:5025092010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51

    Papanastassiou VRampling RFraser MPetty RHadley DNicoll J: 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 9:3984062002

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52

    Parker JNBauer DFCody JJMarkert JM: Oncolytic viral therapy of malignant glioma. Neurotherapeutics 6:5585692009

  • 53

    Perez ODLogg CRHiraoka KDiago OBurnett RInagaki A: Design and selection of Toca 511 for clinical use: modified retroviral replicating vector with improved stability and gene expression. Mol Ther 20:168916982012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 54

    Phuong LKAllen CPeng KWGiannini CGreiner STenEyck CJ: Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme. Cancer Res 63:246224692003

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 55

    Rampling RCruickshank GPapanastassiou VNicoll JHadley DBrennan D: Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther 7:8598662000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56

    Reichard KWLorence RMCascino CJPeeples MEWalter RJFernando MB: Newcastle disease virus selectively kills human tumor cells. J Surg Res 52:4484531992

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57

    Roth JCCassady KACody JJParker JNPrice KHColeman JM: Evaluation of the safety and biodistribution of M032, an attenuated herpes simplex virus type 1 expressing hIL-12, after intracerebral administration to Aotus nonhuman primates. Hum Gene Ther Clin Dev 25:16272014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 58

    Shah ACBenos DGillespie GYMarkert JM: Oncolytic viruses: clinical applications as vectors for the treatment of malignant gliomas. J Neurooncol 65:2032262003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59

    Smitt PSDriesse MWolbers JKros MAvezaat C: Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir. Mol Ther 7:8518582003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60

    Staedtke VBai RYSun WHuang JKibler KKTyler BM: Clostridium novyi-NT can cause regression of orthotopically implanted glioblastomas in rats. Oncotarget 6:553655462015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61

    Stragliotto GRahbar ASolberg NWLilja ATaher COrrego A: Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: a randomized, double-blind, hypothesis-generating study. Int J Cancer 133:120412132013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62

    Strong JETang DLee PWK: Evidence that the epidermal growth factor receptor on host cells confers reovirus infection efficiency. Virology 197:4054111993

  • 63

    Swain J: The treatment of malignant tumours by the toxins of the Streptococcus erysipelatis and Bacillus prodigiosus. BMJ 2:141514161895

  • 64

    Taqi AMAbdurrahman MBYakubu AMFleming AF: Regression of Hodgkin’s disease after measles. Lancet 1:11121981

  • 65

    Trask TWTrask RPAguilar-Cordova EShine HDWyde PRGoodman JC: Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors. Mol Ther 1:1952032000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 66

    Westphal MYlä-Herttuala SMartin JWarnke PMenei PEckland D: Adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir for patients with operable high-grade glioma (ASPECT): a randomised, open-label, phase 3 trial. Lancet Oncol 14:8238332013

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 67

    Wheelock EFDingle JH: Observations on the repeated administration of viruses to a patient with acute leukemia. A preliminary report. N Engl J Med 271:6456511964

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 68

    Wiemann BStarnes CO: Coley’s toxins, tumor necrosis factor and cancer research: a historical perspective. Pharmacol Ther 64:5295641994

  • 69

    Wintrobe MHasenbush L: Chronic leukemia: the early phase of chronic leukemia, the results of treatment and the effects of complicating infections: a study of eighty-six adults. Arch Intern Med 64:7017181939

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 70

    Wollmann GOzduman Kvan den Pol AN: Oncolytic virus therapy for glioblastoma multiforme: concepts and candidates. Cancer J 18:69812012

  • 71

    Xiong WCandolfi MLiu CMuhammad AKYagiz KPuntel M: Human Flt3L generates dendritic cells from canine peripheral blood precursors: implications for a dog glioma clinical trial. PLoS One 5:e110742010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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