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• W3138142132 abstract "•Oncolytic viruses have shown significant promise in glioma management.•Food and Drug Administration (FDA) approval for oncolytic virus in melanoma has accelerated expansion of the field.•FDA has granted Fast Tract Designation for PVSRIPO and DNX2401 in glioma tumors.•A compendium of completed human trials summarizes the development of the field.•Combining oncolytic therapy with other immunotherapeutics is in the future for the field. Gliomas remain one of the more frustrating targets for oncologic therapy. Glioma resistance to conventional therapeutics is a product of their immune-privileged milieu behind the blood-brain barrier, in addition to their suppressive effect on the immune response itself. Taking the lead from the growing success of immunotherapy for systemic cancers, such as lung cancer and melanoma, immunotherapeutics has emerged as a major player in the potential treatment of gliomas, with oncolytic viruses in particular showing significant promise as evidenced by the recent Breakthrough and Fast Tract Designations for PVSRIPO and DNX2401. This review serves as a useful and updated compendium of the completed human clinical investigations for several oncolytic viruses in the treatment of gliomas. Gliomas remain one of the more frustrating targets for oncologic therapy. Glioma resistance to conventional therapeutics is a product of their immune-privileged milieu behind the blood-brain barrier, in addition to their suppressive effect on the immune response itself. Taking the lead from the growing success of immunotherapy for systemic cancers, such as lung cancer and melanoma, immunotherapeutics has emerged as a major player in the potential treatment of gliomas, with oncolytic viruses in particular showing significant promise as evidenced by the recent Breakthrough and Fast Tract Designations for PVSRIPO and DNX2401. This review serves as a useful and updated compendium of the completed human clinical investigations for several oncolytic viruses in the treatment of gliomas. The goal of improving quality of life and prognosis for glioma patients remains the most pressing challenge in neuro-oncology. Standard of care for glioblastoma multiforme (GBM), the most aggressive form of glioma (WHO grade IV), was established in 2005 and includes surgical resection, radiation therapy, and chemotherapy. This regimen, known as the Stupp protocol, has yet to be significantly updated despite median overall survival (OS) of only 12-16 months, reflecting the exceptional resilience of GBM to current treatments.1Stupp R. Mason W.P. van den Bent M.J. et al.Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.N Engl J Med. 2005; 352: 987-996Crossref PubMed Scopus (13181) Google Scholar Tumor treating fields (TTF) was approved in 2011 for recurrent GBM and in 2015 for newly diagnosed GBM. This antimitotic therapy, when added to the Stupp protocol, has shown an OS benefit of 5 months.2Ornelas A.S. Porter A.B. Sharma A. et al.What is the role of tumor-treating fields in newly diagnosed glioblastoma?.Neurologist. 2019; 24: 71-73Crossref PubMed Scopus (5) Google Scholar There has also been a proliferation of genetic markers in GBM that can indicate a more favorable prognosis, such as mutations in IDH1/2 and MGMT promoter methylation, but these have not yet led to targeted medical therapy.3Chiocca E.A. Nassiri F. Wang J. Peruzzi P. Zadeh G. Viral and other therapies for recurrent glioblastoma: is a 24-month durable response unusual?.Neuro Oncol. 2019; 21: 14-25Crossref PubMed Scopus (28) Google Scholar GBMs remain among the most challenging oncologic entities to treat in the human body, as recent progress in extending median survival has been incremental over the last 5-10 years. One promising area of therapeutic innovation for GBM has been immunotherapy. Taking the lead from the success of immunotherapy in other cancers, clinical trials for GBM treatment have increasingly incorporated immunotherapeutic strategies such as replication competent oncolytic viruses (OVs).4Fecci P.E. Sampson J.H. The current state of immunotherapy for gliomas: an eye toward the future.J Neurosurg. 2019; 131: 657-666Crossref PubMed Scopus (41) Google Scholar, 5Lukas R.V. Wainwright D.A. Horbinski C.M. Iwamoto F.M. Sonabend A.M. Immunotherapy against gliomas: is the breakthrough near?.Drugs. 2019; 79: 1839-1848Crossref PubMed Scopus (7) Google Scholar, 6Lynes J. Sanchez V. Dominah G. Nwankwo A. Nduom E. Current options and future directions in immune therapy for glioblastoma.Front Oncol. 2018; 8: 578Crossref PubMed Scopus (15) Google Scholar, 7Miyauchi J.T. Tsirka S.E. Advances in immunotherapeutic research for glioma therapy.J Neurol. 2018; 265: 741-756Crossref PubMed Scopus (43) Google Scholar, 8Csatary L.K. Bakács T. Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma.J Am Med Assoc. 1999; 281: 1588-1589Crossref PubMed Google Scholar Viruses have also been used as vectors for gene therapy; however, this is outside the scope of this article. The mechanism of action of OVs was once thought to be limited to direct oncolysis of cancer cells. In fact, these viruses also have a significant immunomodulatory effect that boosts the immune system antitumor response.4Fecci P.E. Sampson J.H. The current state of immunotherapy for gliomas: an eye toward the future.J Neurosurg. 2019; 131: 657-666Crossref PubMed Scopus (41) Google Scholar,5Lukas R.V. Wainwright D.A. Horbinski C.M. Iwamoto F.M. Sonabend A.M. Immunotherapy against gliomas: is the breakthrough near?.Drugs. 2019; 79: 1839-1848Crossref PubMed Scopus (7) Google Scholar,9Raja J. Ludwig J.M. Gettinger S.N. Schalper K.A. Kim H.S. Oncolytic virus immunotherapy: future prospects for oncology.J Immunother Cancer. 2018; 6: 140Crossref PubMed Scopus (91) Google Scholar,10Samson A. Scott K.J. Taggart D. et al.Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade.Sci Transl Med. 2018; 10: eaam7577Crossref PubMed Scopus (185) Google Scholar To date, the only Food and Drug Administration (FDA)-approved oncolytic viral therapy is talimogene laherparepvec (T-Vec), which was approved in 2015 for metastatic melanoma.9Raja J. Ludwig J.M. Gettinger S.N. Schalper K.A. Kim H.S. Oncolytic virus immunotherapy: future prospects for oncology.J Immunother Cancer. 2018; 6: 140Crossref PubMed Scopus (91) Google Scholar OVs for GBM have shown promise in early-stage trials as highlighted by recent FDA Fast Track Designation for two viruses, PVS-RIPO and DNX-2401, attenuated poliovirus and adenovirus, respectively.11Desjardins A. Herndon 2nd, J.E. McSherry F. et al.Single-institution retrospective review of patients with recurrent glioblastoma treated with bevacizumab in clinical practice.Health Sci Rep. 2019; 2: e114Crossref PubMed Scopus (7) Google Scholar, 12Holl E.K. Brown M.C. Boczkowski D. et al.Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models.Oncotarget. 2016; 7: 79828-79841Crossref PubMed Scopus (29) Google Scholar, 13Philbrick B. Adamson D.C. DNX-2401: an investigational drug for the treatment of recurrent glioblastoma.Expert Opin Investig Drugs. 2019; 28: 1041-1049Crossref PubMed Scopus (16) Google Scholar Clinical trials have been limited to early stage and have not yet fulfilled the potential of their preclinical investigations.14Gesundheit B. Ben-David E. Posen Y. et al.Effective treatment of glioblastoma multiforme with oncolytic virotherapy: a case-series.Front Oncol. 2020; 10: 702Crossref PubMed Scopus (11) Google Scholar OVs are particularly suited for combination therapy with immune checkpoint inhibitors (ICIs) resulting from their immunostimulatory effects. Recent trials have begun to incorporate such combinations.10Samson A. Scott K.J. Taggart D. et al.Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade.Sci Transl Med. 2018; 10: eaam7577Crossref PubMed Scopus (185) Google Scholar,15Markert J.M. Razdan S.N. Kuo H.-C. et al.A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses.Mol Ther. 2014; 22: 1048-1055Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar,16Bernstock J.D. Wright Z. Bag A.K. et al.Stereotactic placement of intratumoral catheters for continuous infusion delivery of herpes simplex virus -1 G207 in pediatric malignant supratentorial brain tumors.World Neurosurg. 2019; 122: e1592-e1598Crossref PubMed Scopus (13) Google Scholar Numerous viruses like Newcastle disease virus (NDV), herpes simplex virus (HSV), reovirus, parvovirus, adenoviruses, and poliovirus have undergone clinical investigation for brain tumors as summarized in Table 1 and Figure 1. The goal of this review is to provide the most up-to-date compendium of existing data on OVs in glioma patients. Our hope is that neuro-oncologists and medical oncologists treating gliomas can use this review as a practical reference for understanding where the field currently stands with OV therapy.Table 1Summary of viruses used in clinical investigations to treat malignant gliomasViruses used in clinical investigation to treat malignant gliomasFeaturesNatural hostRefsNewcastle disease virusSingle-stranded, linear, RNAAvian8Csatary L.K. Bakács T. Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma.J Am Med Assoc. 1999; 281: 1588-1589Crossref PubMed Google Scholar,14Gesundheit B. Ben-David E. Posen Y. et al.Effective treatment of glioblastoma multiforme with oncolytic virotherapy: a case-series.Front Oncol. 2020; 10: 702Crossref PubMed Scopus (11) Google Scholar,18Freeman A.I. Zakay-Rones Z. Gomori J.M. et al.Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.Mol Ther. 2006; 13: 221-228Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar, 19Wagner S. Csatary C.M. Gosztonyi G. et al.Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid.APMIS. 2006; 114: 731-743Crossref PubMed Scopus (37) Google Scholar, 20Csatary L.K. Gosztonyi G. Szeberenyi J. et al.MTH-68/H oncolytic viral treatment in human high-grade gliomas.J Neurooncol. 2004; 67: 83-93Crossref PubMed Scopus (143) Google ScholarReovirusDouble-stranded, linear, DNAHuman10Samson A. Scott K.J. Taggart D. et al.Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade.Sci Transl Med. 2018; 10: eaam7577Crossref PubMed Scopus (185) Google Scholar,14Gesundheit B. Ben-David E. Posen Y. et al.Effective treatment of glioblastoma multiforme with oncolytic virotherapy: a case-series.Front Oncol. 2020; 10: 702Crossref PubMed Scopus (11) Google Scholar,51Kicielinski K.P. Chiocca E.A. Yu J.S. Gill G.M. Coffey M. Markert J.M. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults.Mol Ther. 2014; 22: 1056-1062Abstract Full Text Full Text PDF PubMed Scopus (70) Google ScholarParvovirusSingle-stranded, linear, DNARat14Gesundheit B. Ben-David E. Posen Y. et al.Effective treatment of glioblastoma multiforme with oncolytic virotherapy: a case-series.Front Oncol. 2020; 10: 702Crossref PubMed Scopus (11) Google Scholar,59Geletneky K. Hajda J. Angelova A.L. et al.Oncolytic H-1 parvovirus shows safety and signs of immunogenic activity in a first phase I/IIa glioblastoma trial.Mol Ther. 2017; 25: 2620-2634Abstract Full Text Full Text PDF PubMed Scopus (106) Google ScholarAdenovirusDouble-stranded, linear DNAHuman54Chiocca E.A. Abbed K.M. Tatter S. et al.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. 2004; 10: 958-966Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar,56Lang F.F. Conrad C. Gomez-Manzano C. et al.Phase I study of DNX-2401 (Delta-24-RGD) oncolytic adenovirus: replication and immunotherapeutic effects in recurrent malignant glioma.J Clin Oncol. 2018; 36: 1419-1427Crossref PubMed Scopus (238) Google Scholar,81Lang F.F. Tran N.D. Puduvalli V.K. et al.Phase 1b open-label randomized study of the oncolytic adenovirus DNX-2401 administered with or without interferon gamma for recurrent glioblastoma.J Clin Oncol. 2017; 35: 2002Crossref Google ScholarPoliovirusSingle-stranded, linear RNAHuman45Desjardins A. Gromeier M. Herndon 2nd, J.E. et al.Recurrent glioblastoma treated with recombinant poliovirus.N Engl J Med. 2018; 379: 150-161Crossref PubMed Scopus (279) Google ScholarVaccinia virusDouble-stranded, linear DNAHuman14Gesundheit B. Ben-David E. Posen Y. et al.Effective treatment of glioblastoma multiforme with oncolytic virotherapy: a case-series.Front Oncol. 2020; 10: 702Crossref PubMed Scopus (11) Google ScholarHerpes simples virusDouble-stranded, linear DNAHuman15Markert J.M. Razdan S.N. Kuo H.-C. et al.A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses.Mol Ther. 2014; 22: 1048-1055Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar,35Rampling R. Cruickshank G. Papanastassiou V. et al.Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma.Gene Ther. 2000; 7: 859-866Crossref PubMed Scopus (503) Google Scholar, 36Papanastassiou V. Rampling R. Fraser M. et al.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. 2002; 9: 398-406Crossref PubMed Scopus (260) Google Scholar, 37Markert J.M. Medlock M.D. Rabkin S.D. et al.Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial.Gene Ther. 2000; 7: 867-874Crossref PubMed Scopus (781) Google Scholar, 38Markert J.M. Liechty P.G. Wang W. et al.Phase Ib trial of mutant herpes simplex virus G207 inoculated pre-and post-tumor resection for recurrent GBM.Mol Ther. 2009; 17: 199-207Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar,43Harrow S. Papanastassiou V. Harland J. et al.HSV1716 injection into the brain adjacent to tumour following surgical resection of high-grade glioma: safety data and long-term survival.Gene Ther. 2004; 11: 1648-1658Crossref PubMed Scopus (264) Google Scholar Open table in a new tab NDV is a spherical paramyxovirus with an avian natural host.17Tayeb S. Zakay-Rones Z. Panet A. Therapeutic potential of oncolytic Newcastle disease virus: a critical review.Oncolytic Virother. 2015; 4: 49-62PubMed Google Scholar Its mechanism is via selective lysis of cancer cells and promotion of an antitumor inflammatory response. To date, there have been two types of NDV that have been used in glioma treatment: MTH-68/H, a mesogenic strain, and NDV-HUJ, a lentogenic strain8Csatary L.K. Bakács T. Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma.J Am Med Assoc. 1999; 281: 1588-1589Crossref PubMed Google Scholar,17Tayeb S. Zakay-Rones Z. Panet A. Therapeutic potential of oncolytic Newcastle disease virus: a critical review.Oncolytic Virother. 2015; 4: 49-62PubMed Google Scholar, 18Freeman A.I. Zakay-Rones Z. Gomori J.M. et al.Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.Mol Ther. 2006; 13: 221-228Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar, 19Wagner S. Csatary C.M. Gosztonyi G. et al.Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid.APMIS. 2006; 114: 731-743Crossref PubMed Scopus (37) Google Scholar, 20Csatary L.K. Gosztonyi G. Szeberenyi J. et al.MTH-68/H oncolytic viral treatment in human high-grade gliomas.J Neurooncol. 2004; 67: 83-93Crossref PubMed Scopus (143) Google Scholar (Table 2). The safety and oncolytic effects of NDV are based on conditional replication in cancer cells and not in normal cells, which was demonstrated in 1988 and again in 2006.21Lorence R.M. Rood P.A. Kelley K.W. Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-alpha and augmentation of its cytotoxicity.J Natl Cancer Inst. 1988; 80: 1305-1312Crossref PubMed Scopus (144) Google Scholar,22Krishnamurthy S. Takimoto T. Scroggs R.A. Portner A. Differentially regulated interferon response determines the outcome of Newcastle disease virus infection in normal and tumor cell lines.J Virol. 2006; 80: 5145-5155Crossref PubMed Scopus (125) Google Scholar Likewise, Lorence et al.23Lorence R.M. Roberts M.S. O'Neil J.D. et al.Phase 1 clinical experience using intravenous administration of PV701, an oncolytic Newcastle disease virus.Curr Cancer Drug Targets. 2007; 7: 157-167Crossref PubMed Scopus (84) Google Scholar in 2007 proposed that cancer cells are more sensitive to NDV infection because cancer cells are generally defective in interferon (IFN) responses compared with a normal equivalent cell. Like MTH-68/H, NDV-HUJ also has been reported to rely on induction of apoptosis in glioma.18Freeman A.I. Zakay-Rones Z. Gomori J.M. et al.Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.Mol Ther. 2006; 13: 221-228Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar The mechanism for tumor regression after NDV has yet to be fully elucidated, though several pathways have been proposed: induction of apoptosis, direct tumor lysis, enhanced tumor-specific immune response, and cytokine release.18Freeman A.I. Zakay-Rones Z. Gomori J.M. et al.Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.Mol Ther. 2006; 13: 221-228Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar,24Csatary L.K. Eckhardt S. Bukosza I. et al.Attenuated veterinary virus vaccine for the treatment of cancer.Cancer Detect Prev. 1993; 17: 619-627PubMed Google Scholar Cytokines such as tumor necrosis factor (TNF), IFNs, interleukin-6, and interleukin-10 have been recognized to enhance tumor immunity.24Csatary L.K. Eckhardt S. Bukosza I. et al.Attenuated veterinary virus vaccine for the treatment of cancer.Cancer Detect Prev. 1993; 17: 619-627PubMed Google Scholar A more recent molecular pathway analysis describes NDV activating intrinsic death pathway, eIF2a kinase protein kinase R-like endoplasmic reticulum kinase and caspase 12, and TNF-related apoptosis inducing ligand.17Tayeb S. Zakay-Rones Z. Panet A. Therapeutic potential of oncolytic Newcastle disease virus: a critical review.Oncolytic Virother. 2015; 4: 49-62PubMed Google Scholar AA, anaplastic astrocytoma; CT, chemotherapy; GBM, glioblastoma multiforme; I.A., intra-arterial; I.V., intravenous; NDV, Newcastle disease virus; OA, oligoastrocytoma; OS, overall survival; RT, radiation therapy; S, surgery; WT, wild-type. The MTH-68/H strain was developed from the Hertfordshire NDV strain and was first used in metastatic carcinoma in 1968.25Csatary L.K. Moss R.W. Beuth J. Töröcsik B. Szeberenyi J. Bakacs T. Beneficial treatment of patients with advanced cancer using a Newcastle disease virus vaccine (MTH-68/H).Anticancer Res. 1999; 19: 635-638PubMed Google Scholar Trials for central nervous system (CNS) tumors began in 1999.8Csatary L.K. Bakács T. Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma.J Am Med Assoc. 1999; 281: 1588-1589Crossref PubMed Google Scholar In all three reports, MTH-68/H is administered intravenously (i.v.) in adult and pediatric patients with recurrent GBM and anaplastic astrocytoma (AA) refractory to surgery, radiation therapy, and chemotherapy and found to have a median OS of 3-5 years.8Csatary L.K. Bakács T. Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma.J Am Med Assoc. 1999; 281: 1588-1589Crossref PubMed Google Scholar,19Wagner S. Csatary C.M. Gosztonyi G. et al.Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid.APMIS. 2006; 114: 731-743Crossref PubMed Scopus (37) Google Scholar,20Csatary L.K. Gosztonyi G. Szeberenyi J. et al.MTH-68/H oncolytic viral treatment in human high-grade gliomas.J Neurooncol. 2004; 67: 83-93Crossref PubMed Scopus (143) Google Scholar Csatary and Bakács8Csatary L.K. Bakács T. Use of Newcastle disease virus vaccine (MTH-68/H) in a patient with high-grade glioblastoma.J Am Med Assoc. 1999; 281: 1588-1589Crossref PubMed Google Scholar and Csatary et al.20Csatary L.K. Gosztonyi G. Szeberenyi J. et al.MTH-68/H oncolytic viral treatment in human high-grade gliomas.J Neurooncol. 2004; 67: 83-93Crossref PubMed Scopus (143) Google Scholar reported two case series in 1999 and 2004 where adult and pediatric patients experienced survival of 3 years and 5-9 years, respectively, with MTH-68/H as their only form of therapy. The 2004 report also commented on increased efficacy with the i.v. dosing as compared with inhalational administration.20Csatary L.K. Gosztonyi G. Szeberenyi J. et al.MTH-68/H oncolytic viral treatment in human high-grade gliomas.J Neurooncol. 2004; 67: 83-93Crossref PubMed Scopus (143) Google Scholar The group reported increased clinical efficacy with increased i.v. dosing and decreased frequency of administration. Wagner et al.19Wagner S. Csatary C.M. Gosztonyi G. et al.Combined treatment of pediatric high-grade glioma with the oncolytic viral strain MTH-68/H and oral valproic acid.APMIS. 2006; 114: 731-743Crossref PubMed Scopus (37) Google Scholar in 2006 later reported a case of a thalamic AA in a boy treated with i.v. and/or inhalational MTH-68/H and oral valproic acid. The tumor shrank to 15% of its original size, yet soon recurred in the 4th ventricle requiring surgery. This was the first study that demonstrated abundant accumulation of apoptotic tumor cell nuclei in a histological analysis after 5 months of continuous NDV treatment. They also first demonstrated virus replication within the tumor by the presence of NDV-like particles in the neoplastic cells. In all three studies with MTH-68/H, no adverse events due to virus administration were reported. It is unclear why additional trials were not conducted, despite these encouraging results. NDV-HJU is also under investigation.18Freeman A.I. Zakay-Rones Z. Gomori J.M. et al.Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.Mol Ther. 2006; 13: 221-228Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar In 2006, Freeman et al.18Freeman A.I. Zakay-Rones Z. Gomori J.M. et al.Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.Mol Ther. 2006; 13: 221-228Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar reported a phase I/II dose escalation study. I.V. administration of NDV-HUJ was used in 14 patients aged 11-58 years with recurrent GBM refractory to surgery, radiation therapy, and chemotherapy. In this case series, one patient achieved a complete response with adverse events limited to grade 1/2 constitutional fevers.18Freeman A.I. Zakay-Rones Z. Gomori J.M. et al.Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme.Mol Ther. 2006; 13: 221-228Abstract Full Text Full Text PDF PubMed Scopus (262) Google Scholar Given that the i.v. administration was well tolerated with encouraging results, NDV-JHU warrants continued investigation for GBM. Currently, there are no active clinical trials using NDV though there has been promising basic science research demonstrating its utility in both in vivo and in vitro models.26Cuoco J.A. Rogers C.M. Mittal S. The oncolytic Newcastle disease virus as an effective immunotherapeutic strategy against glioblastoma.Neurosurg Focus. 2021; 50: E8Crossref PubMed Scopus (3) Google Scholar, 27García-Romero N. Palacín-Aliana I. Esteban-Rubio S. et al.Newcastle disease virus (NDV) oncolytic activity in human glioma tumors is dependent on CDKN2A-Type I IFN gene cluster codeletion.Cells. 2020; 9: 1405Crossref Scopus (7) Google Scholar, 28Bai Y. Chen Y. Hong X. et al.Newcastle disease virus enhances the growth-inhibiting and proapoptotic effects of temozolomide on glioblastoma cells in vitro and in vivo.Sci Rep. 2018; 8: 11470Crossref PubMed Scopus (22) Google Scholar HSVs are perhaps the most widely characterized OVs with six completed clinical reports in gliomas to date (Table 3). HSV viruses remain leading candidates in glioma treatment given the recent success and FDA approval of T-Vec in 2015 for melanoma. As is the case with NDV, the antitumor effect of oncolytic HSV is twofold: direct cytolysis followed by recruitment of an immune response. As mentioned, the genetic alterations allow conditional replication of oncolytic HSVs. This allows preferential viral replication in tumor cells and subsequent lysis further propagating local spread of the virus. Viral entry relies on one of three classes of membrane receptors.29Totsch S.K. Schlappi C. Kang K.-D. et al.Oncolytic herpes simplex virus immunotherapy for brain tumors: current pitfalls and emerging strategies to overcome therapeutic resistance.Oncogene. 2019; 38: 6159-6171Crossref PubMed Scopus (25) Google Scholar,30Friedman G.K. Bernstock J.D. Chen D. et al.Enhanced sensitivity of patient-derived pediatric high-grade brain tumor xenografts to oncolytic HSV-1 virotherapy correlates with nectin-1 expression.Sci Rep. 2018; 8: 13930Crossref PubMed Scopus (26) Google Scholar Once tumor cells are lysed, there is a release of tumor-associated antigens which leads to induction of local and systemic antitumor immunity.31Yin J. Markert J.M. Leavenworth J.W. Modulation of the intratumoral immune landscape by oncolytic herpes simplex virus virotherapy.Front Oncol. 2017; 7: 136Crossref PubMed Scopus (26) Google Scholar The success of viral propagation depends on a delicate balance between the hosts antiviral response versus its antitumor response. Oncolytic HSV administered in the brain induces immediate recruitment and activation of natural killer cells, macrophages, and microglia, which account for viral clearance and blunting of the antitumor efficacy of oncolytic HSV.32Hua L. Wakimoto H. Oncolytic herpes simplex virus therapy for malignant glioma: current approaches to successful clinical application.Expert Opin Biol Ther. 2019; 19: 845-854Crossref PubMed Scopus (11) Google Scholar There is now evidence that antiviral responses also contribute to antitumor efficacy despite slowing viral replication as summarized in Figure 2.33Cassady K.A. Haworth K.B. Jackson J. Markert J.M. Cripe T.P. To infection and beyond: the multi-pronged anti-cancer mechanisms of oncolytic viruses.Viruses. 2016; 8: 43Crossref PubMed Scopus (32) Google Scholar As oncolytic HSV triggers an innate immune response, adaptive immune responses have also been characterized.32Hua L. Wakimoto H. Oncolytic herpes simplex virus therapy for malignant glioma: current approaches to successful clinical application.Expert Opin Biol Ther. 2019; 19: 845-854Crossref PubMed Scopus (11) Google Scholar The immunogenic death of infected cells releases pathogen-associated molecular patterns and damage-associated molecular patterns that could facilitate dendritic cell presentation to T cells.32Hua L. Wakimoto H. Oncolytic herpes simplex virus therapy for malignant glioma: current approaches to successful clinical application.Expert Opin Biol Ther. 2019; 19: 845-854Crossref PubMed Scopus (11) Google Scholar Efficacy of cellular immunity is often limited due to the immunologically suppressive microenvironment of grade III and IV gliomas. Numerous studies are underway addressing these challenges. AA, anaplastic astrocytoma; CT, chemotherapy; GBM, glioblastoma multiforme; HSV, herpes simplex virus; I.T., intratumoral; OA, oligoastrocytoma; OS, overall survival; RT, radiation therapy; S, surgery; TTP, time to progression. Normal cells are resistant to infection while conditional replication is limited to tumor cells due to specific tropism. Once infected, tumor cells are susceptible to cell death, which leads to propagation and viral replication. Subsequently, both the innate and adaptive immune responses are recruited to the tumor. While it is thought the main antitumor effect is derived from the immune response, it also has the potential, however, to inactivate the circulating virus and in fact blunt viral replication and propagation. Martuza et al.34Martuza R.L. Malick A. Markert J.M. Ruffner K.L. Coen D.M. Experimental therapy of human glioma by means of a genetically engineered virus mutant.Science. 1991; 252: 854-856Crossref PubMed Scopus (737) Google Scholar in 1991 provided the first report of a recombinant HSV specifically targeting the U87 human GBM cell line and demonstrated attenuating neurovirulence in non-dividing cells. Currently, there are two recombinant HSVs that have undergone clinical investigation, as summarized in Table 3: HSV1716 and HSVG207.15Markert J.M. Razdan S.N. Kuo H.-C. et al.A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses.Mol Ther. 2014; 22: 1048-1055Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar,35Rampling R. Cruickshank G. Papanastassiou V. et al.Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignan" @default.
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• W3138142132 title "Oncolytic virus in gliomas: a review of human clinical investigations" @default.
• W3138142132 cites W1970718186 @default.
• W3138142132 cites W1971532562 @default.
• W3138142132 cites W1972455109 @default.
• W3138142132 cites W1983766005 @default.
• W3138142132 cites W1984087096 @default.
• W3138142132 cites W1987741335 @default.
• W3138142132 cites W2008393860 @default.
• W3138142132 cites W2018535642 @default.
• W3138142132 cites W2018648852 @default.
• W3138142132 cites W2026406742 @default.
• W3138142132 cites W2037171350 @default.
• W3138142132 cites W2038709470 @default.
• W3138142132 cites W2049092411 @default.
• W3138142132 cites W2050216826 @default.
• W3138142132 cites W2057382033 @default.
• W3138142132 cites W2059888157 @default.
• W3138142132 cites W2073134590 @default.
• W3138142132 cites W2078103037 @default.
• W3138142132 cites W2079935861 @default.
• W3138142132 cites W2080496139 @default.
• W3138142132 cites W2092207202 @default.
• W3138142132 cites W2094949672 @default.
• W3138142132 cites W2096287682 @default.
• W3138142132 cites W2097050869 @default.
• W3138142132 cites W2114544688 @default.
• W3138142132 cites W2165528562 @default.
• W3138142132 cites W2169810189 @default.
• W3138142132 cites W2192594451 @default.
• W3138142132 cites W2252869735 @default.
• W3138142132 cites W2313228602 @default.
• W3138142132 cites W2539571618 @default.
• W3138142132 cites W2622931261 @default.
• W3138142132 cites W2651033244 @default.
• W3138142132 cites W2677916979 @default.
• W3138142132 cites W2748217844 @default.
• W3138142132 cites W2748739447 @default.
• W3138142132 cites W2756123402 @default.
• W3138142132 cites W2763265527 @default.
• W3138142132 cites W2781931068 @default.
• W3138142132 cites W2787278337 @default.
• W3138142132 cites W2806726370 @default.
• W3138142132 cites W2811300508 @default.
• W3138142132 cites W2854847149 @default.
• W3138142132 cites W2884990513 @default.
• W3138142132 cites W2891755039 @default.
• W3138142132 cites W2897975460 @default.
• W3138142132 cites W2901574198 @default.
• W3138142132 cites W2902146996 @default.
• W3138142132 cites W2902180413 @default.
• W3138142132 cites W2911455769 @default.
• W3138142132 cites W2911752971 @default.
• W3138142132 cites W2913623258 @default.
• W3138142132 cites W2913851162 @default.
• W3138142132 cites W2919812572 @default.
• W3138142132 cites W2941968547 @default.
• W3138142132 cites W2942815582 @default.
• W3138142132 cites W2953098645 @default.
• W3138142132 cites W2957488658 @default.
• W3138142132 cites W2979715801 @default.
• W3138142132 cites W2981504474 @default.
• W3138142132 cites W2982946489 @default.
• W3138142132 cites W3001089839 @default.
• W3138142132 cites W3022191219 @default.
• W3138142132 cites W3025534925 @default.
• W3138142132 cites W3026551532 @default.
• W3138142132 cites W3033014431 @default.
• W3138142132 cites W3080269137 @default.
• W3138142132 cites W3114158415 @default.
• W3138142132 cites W3120974102 @default.
• W3138142132 cites W3124821786 @default.
• W3138142132 cites W3126562453 @default.
• W3138142132 cites W3127383553 @default.
• W3138142132 cites W3127856397 @default.
• W3138142132 cites W3128464309 @default.
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