297
Views
0
CrossRef citations to date
0
Altmetric
Review

Oncolytic virus therapy for malignant gliomas: entering the new era

ORCID Icon & ORCID Icon
Pages 269-282 | Received 26 Nov 2022, Accepted 21 Feb 2023, Published online: 02 Mar 2023

References

  • Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987–996.
  • van Linde ME, Brahm CG, de Witt Hamer PC, et al. Treatment outcome of patients with recurrent glioblastoma multiforme: a retrospective multicenter analysis. J Neurooncol. 2017 Oct;135(1):183–192.
  • Achard C, Surendran A, Wedge ME, et al. Lighting a Fire in the Tumor Microenvironment Using Oncolytic Immunotherapy. EBioMedicine. 2018 May;31:17–24.
  • Todo T, Ito H, Ino Y, et al. Intratumoral oncolytic herpes virus G47 for residual or recurrent glioblastoma: a phase 2 trial. Nat Med. 2022 Aug;28(8):1630–1639.
  • Lauer UM, Beil J. Oncolytic viruses: challenges and considerations in an evolving clinical landscape. Future Oncol. 2022 Jul;12.
  • Masemann D, Boergeling Y, Employing LS. RNA viruses to fight cancer: novel insights into oncolytic virotherapy. Biol Chem. 2017 Jul 26;398(8):891–909.
  • Geletneky K, Hajda J, Angelova AL, et al. Oncolytic H-1 Parvovirus Shows Safety and Signs of Immunogenic Activity in a First Phase I/IIa Glioblastoma Trial. Mol Ther. 2017 Dec 6;25(12):2620–2634.
  • Peng KW, Facteau S, Wegman T, et al. Non-invasive in vivo monitoring of trackable viruses expressing soluble marker peptides. Nat Med. 2002 May;8(5):527–531.
  • Phuong LK, Allen C, Peng KW, et al. Use of a vaccine strain of measles virus genetically engineered to produce carcinoembryonic antigen as a novel therapeutic agent against glioblastoma multiforme. Cancer Res. 2003 May 15;63(10):2462–2469.
  • Allen C, Opyrchal M, Aderca I, et al. Oncolytic measles virus strains have significant antitumor activity against glioma stem cells. Gene Ther. 2013 Apr;20(4):444–449.
  • MacLean AR, ul-Fareed M, Robertson L, et al. Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+ between immediate early gene 1 and the ‘a’ sequence. J Gen Virol. 1991 Mar;72(Pt 3):631–639.
  • Harrow 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;Nov;11(22):1648–1658.
  • Papanastassiou 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 Mar 9;9(6):398–406.
  • Rampling 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 May;7(10):859–866.
  • Mineta T, Rabkin SD, Yazaki T, et al. Attenuated multi–mutated herpes simplex virus–1 for the treatment of malignant gliomas. Nat Med. 1995 Sep;1(9):938–943.
  • Markert JM, Medlock MD, Rabkin SD, et al. Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase I trial. Gene Ther. 2000 May;7(10):867–874.
  • Markert JM, Liechty PG, 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 Jan;17(1):199–207.
  • Todo T, Martuza RL, Rabkin SD, et al. Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc Natl Acad Sci U S A. 2001 May 22;98(11):6396–6401.
  • Todo T, Ino Y, Ohtsu H, et al. A phase I/II study of triple-mutated oncolytic herpes virus G47∆ in patients with progressive glioblastoma. Nat Commun. 2022 Jul 21;13(1):4119.
  • Chiocca EA, Nakashima H, Kasai K, et al. Preclinical Toxicology of rQNestin34.5v.2: An Oncolytic Herpes Virus with Transcriptional Regulation of the ICP34.5 Neurovirulence Gene. Mol Ther Methods Clin Dev. 2020 Jun 12;17:871–893.
  • Patel DM, Foreman PM, Nabors LB, et al. 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. Hum Gene Ther Clin Dev. 2016 Jun;27(2):69–78.
  • Cassady KA, Bauer DF, Roth J, et al. Pre-clinical Assessment of C134, a Chimeric Oncolytic Herpes Simplex Virus, in Mice and Non-human Primates. Mol Ther Oncolytics. 2017 Jun 16;5:1–10.
  • Bischoff JR, Kirn DH, Williams A, et al. An Adenovirus Mutant That Replicates Selectively in p53- Deficient Human Tumor Cells. Science. 1996 Oct 18;274(5286):373–376.
  • Chiocca EA, Abbed KM, 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 Nov;10(5):958–966.
  • Suzuki K, Fueyo J, Krasnykh V, et al. A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res. 2001 Jan;7(1):120–126.
  • Lang FF, 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 May 10;36(14):1419–1427.
  • van Putten EHP, Kleijn A, van Beusechem VW, et al. Convection Enhanced Delivery of the Oncolytic Adenovirus Delta24-RGD in Patients with Recurrent GBM: A Phase I Clinical Trial Including Correlative Studies. Clin Cancer Res. 2022 Apr 14;28(8):1572–1585.
  • Chen SR, Chen MM, Ene C, et al. Perfusion-guided endovascular super-selective intra-arterial infusion for treatment of malignant brain tumors. J Neurointerv Surg. 2022 Jun;14(6):533–538.
  • Jiang H, Rivera-Molina Y, Gomez-Manzano C, et al. Oncolytic Adenovirus and Tumor-Targeting Immune Modulatory Therapy Improve Autologous Cancer Vaccination. Cancer Res. 2017 Jul 15;77(14):3894–3907.
  • Puigdelloses M, Garcia-Moure M, Labiano S, et al. CD137 and PD-L1 targeting with immunovirotherapy induces a potent and durable antitumor immune response in glioblastoma models.J Immunother Cancer.2021;97:Jul
  • Foloppe J, Kempf J, Futin N, et al. The Enhanced Tumor Specificity of TG6002, an Armed Oncolytic Vaccinia Virus Deleted in Two Genes Involved in Nucleotide Metabolism. Mol Ther Oncolytics. 2019 Sep 27;14:1–14.
  • Idbaih A, Erbs P, Foloppe J, et al. TG6002: A novel oncolytic and vectorized gene pro-drug therapy approach to treat glioblastoma. J Clin Oncol. 2017;35(15_suppl):e13510–e13510.
  • Gromeier M, Alexander L, Wimmer E. Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants. Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2370–2375.
  • Chandramohan V, Bryant JD, Piao H, et al. Validation of an Immunohistochemistry Assay for Detection of CD155, the Poliovirus Receptor, in Malignant Gliomas. Arch Pathol Lab Med. 2017 Dec;141(12):1697–1704.
  • Desjardins A, Gromeier M, Herndon JE 2nd, et al. Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med. 2018 Jul 12;379(2):150–161.
  • Forsyth P, Roldan G, George D, et al. A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas. Mol Ther. 2008 Mar;16(3):627–632.
  • Kicielinski KP, Chiocca EA, Yu JS, et al. Phase 1 clinical trial of intratumoral reovirus infusion for the treatment of recurrent malignant gliomas in adults. Mol Ther. 2014 May;22(5):1056–1062.
  • Samson A, Scott KJ, Taggart D, et al. Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade. Sci Transl Med. 2018;10:Jan 3422.
  • Advani SJ, Markert JM, Sood RF, et al. Increased oncolytic efficacy for high-grade gliomas by optimal integration of ionizing radiation into the replicative cycle of HSV-1. Gene Ther. 2011 Nov;18(11):1098–1102.
  • Markert JM, Razdan SN, Kuo HC, 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 May;22(5):1048–1055.
  • Aghi M, Rabkin S, Martuza RL. Effect of chemotherapy-induced DNA repair on oncolytic herpes simplex viral replication. J Natl Cancer Inst. 2006 Jan 4;98(1):38–50.
  • Saha D, Rabkin SD, Martuza RL May. Temozolomide antagonizes oncolytic immunovirotherapy in glioblastoma. J Immunother Cancer. 2020;8:1.
  • Kleijn A, van den Bossche W, Haefner ES, et al. The Sequence of Delta24-RGD and TMZ Administration in Malignant Glioma Affects the Role of CD8(+)T Cell Anti-tumor Activity. Mol Ther Oncolytics. 2017 Jun 16;5:11–19.
  • Alonso MM, García-Moure M, Gonzalez-Huarriz M, et al. Abstract CT027: Oncolytic virus DNX-2401 with a short course of temozolomide for glioblastoma at first recurrence: Clinical data and prognostic biomarkers. Cancer Res. 2017;77(13_Supplement):CT027–CT027.
  • Zadeh G. LTBK-04. PHASE 2 multicenter study of the oncolytic adenovirus DNX-2401 (TASADENOTUREV) in combination with pembrolizumab for recurrent glioblastoma; captive study (KEYNOTE-192). Neuro Oncol. 2020;22(Supplement_2):237.
  • Lang FF, Tran ND, Puduvalli VK, 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(15_suppl):2002.
  • Ulasov IV, Zhu ZB, Tyler MA, et al. Survivin-driven and fiber-modified oncolytic adenovirus exhibits potent antitumor activity in established intracranial glioma. Hum Gene Ther. 2007 Jul;18(7):589–602.
  • Fares J, Ahmed AU, Ulasov IV, et al. Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial. Lancet Oncol. 2021;22(8):1103–1114.
  • Friedman GK, Bernstock JD, 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 Sep 17;8(1):13930.
  • Friedman GK, Johnston JM, Bag AK, et al. Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas. N Engl J Med. 2021 Apr 29;384(17):1613–1622.
  • Bernstock JD, Bag AK, Fiveash J, et al. Design and Rationale for First-in-Human Phase 1 Immunovirotherapy Clinical Trial of Oncolytic HSV G207 to Treat Malignant Pediatric Cerebellar Brain Tumors. Hum Gene Ther. 2020 Oct;31(19–20):1132–1139.
  • Schuelke MR, Gundelach JH, Coffey M, et al. Phase I trial of sargramostim/pelareorep therapy in pediatric patients with recurrent or refractory high-grade brain tumors. Neurooncol Adv. 2022 Jan-Dec;4(1):vdac085.
  • Gallego Perez-Larraya J, Garcia-Moure M, Labiano S, et al. Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma. N Engl J Med. 2022 Jun 30;386(26):2471–2481.
  • Saha D, Martuza RL, Rabkin SD. Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade. Cancer Cell. 2017 Aug 14;32(2):253–267 e5.
  • Passaro C, Alayo Q, De Laura I, et al. Arming an Oncolytic Herpes Simplex Virus Type 1 with a Single-chain Fragment Variable Antibody against PD-1 for Experimental Glioblastoma Therapy. Clin Cancer Res. 2019 Jan 1;25(1):290–299.
  • Xu B, Tian L, Chen J, et al. An oncolytic virus expressing a full-length antibody enhances antitumor innate immune response to glioblastoma. Nat Commun. 2021 Oct 8;12(1):5908.
  • Tian L, Xu B, Chen Y, et al. Specific targeting of glioblastoma with an oncolytic virus expressing a cetuximab-CCL5 fusion protein via innate and adaptive immunity. Nat Cancer. 2022;3(11):1318–1335.
  • Waldmann TA, Tagaya Y. The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu Rev Immunol. 1999;17:19–49.
  • Fehniger TA, Cooper MA, Caligiuri MA. Interleukin-2 and interleukin-15: immunotherapy for cancer. Cytokine Growth Factor Rev. 2002;13(2):169–183.
  • Zhang Q, Zhang J, Tian Y, et al. Efficacy of a novel double-controlled oncolytic adenovirus driven by the Ki67 core promoter and armed with IL-15 against glioblastoma cells. Cell Biosci. 2020;10:124.
  • Zhang Q, Zhang J, Wang P, et al. Glioma-associated mesenchymal stem cells-mediated PD-L1 expression is attenuated by Ad5-Ki67/IL-15 in GBM treatment. Stem Cell Res Ther. 2022 Jun 28;13(1):284.
  • Russell L, Swanner J, Jaime-Ramirez AC, et al. PTEN expression by an oncolytic herpesvirus directs T-cell mediated tumor clearance. Nat Commun. 2018 Nov 27;9(1):5006.
  • Payne LS, Huang PH. The pathobiology of collagens in glioma. Mol Cancer Res. 2013 Oct;11(10):1129–1140.
  • Sette P, Amankulor N, Li A, et al. GBM-Targeted oHSV Armed with Matrix Metalloproteinase 9 Enhances Anti-tumor Activity and Animal Survival. Mol Ther Oncolytics. 2019 Dec 20;15:214–222.
  • Mohiuddin E, Wakimoto H. Extracellular matrix in glioblastoma: opportunities for emerging therapeutic approaches. Am J Cancer Res. 2021;11(8):3742–3754.
  • Kiyokawa J, Kawamura Y, Ghouse SM, et al. Modification of Extracellular Matrix Enhances Oncolytic Adenovirus Immunotherapy in Glioblastoma. Clin Cancer Res. 2021 Feb 1;27(3):889–902.
  • Li M, Li G, Kiyokawa J, et al. Characterization and oncolytic virus targeting of FAP-expressing tumor-associated pericytes in glioblastoma. Acta Neuropathol Commun. 2020 Dec 11;8(1):221.
  • Ma R, Lu T, Li Z, et al. An Oncolytic Virus Expressing IL15/IL15Ralpha Combined with Off-the-Shelf EGFR-CAR NK Cells Targets Glioblastoma. Cancer Res. 2021 Jul 1;81(13):3635–3648.
  • Zhu G, Zhang J, Zhang Q, et al. Enhancement of CD70-specific CAR T treatment by IFN-gamma released from oHSV-1-infected glioblastoma. Cancer Immunol Immunother. 2022 Oct;71(10):2433–2448.
  • Chalise L, Kato A, Ohno M, et al. Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47Delta combination therapy against glioblastoma. Mol Ther Oncolytics. 2022 Sep 15;26:265–274.
  • Wang G, Zhang Z, Zhong K, et al. CXCL11-armed oncolytic adenoviruses enhance CAR-T cell therapeutic efficacy and reprogram tumor microenvironment in glioblastoma. Mol Ther. 2022;31(1):134–153.
  • Fukuhara H, Takeshima Y, Todo T. Triple-mutated oncolytic herpes virus for treating both fast- and slow-growing tumors. Cancer Sci. 2021 Aug;112(8):3293–3301.
  • Kim CY, Jeong M, Mushiake H, et al. Cancer gene therapy using a novel secretable trimeric TRAIL. Gene Ther. 2006 Feb;13(4):330–338.
  • Oh E, Hong J, Kwon OJ, et al. A hypoxia- and telomerase-responsive oncolytic adenovirus expressing secretable trimeric TRAIL triggers tumour-specific apoptosis and promotes viral dispersion in TRAIL-resistant glioblastoma. Sci Rep. 2018 Jan 23;8(1):1420.
  • Sanchez Gil J, Dubois M, Neirinckx V, et al. Nanobody-based retargeting of an oncolytic herpesvirus for eliminating CXCR4(+) GBM cells: A proof of principle. Mol Ther Oncolytics. 2022 Sep 15;26:35–48.
  • Jiang H, Gomez-Manzano C, Aoki H, et al. Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death. J Natl Cancer Inst. 2007 Sep 19;99(18):1410–1414.
  • Wakimoto H, Kesari S, Farrell CJ, et al. Human glioblastoma-derived cancer stem cells: establishment of invasive glioma models and treatment with oncolytic herpes simplex virus vectors. Cancer Res. 2009 Apr 15;69(8):3472–3481.
  • Peters C, Paget M, Tshilenge KT, et al. Restriction of Replication of Oncolytic Herpes Simplex Virus with a Deletion of gamma34.5 in Glioblastoma Stem-Like Cells. J Virol. 2018 Aug 1;92:15.
  • Bach P, Abel T, Hoffmann C, et al. Specific elimination of CD133+ tumor cells with targeted oncolytic measles virus. Cancer Res. 2013 Jan 15;73(2):865–874.
  • Menotti L, Avitabile E, Gatta V, et al. HSV as A Platform for the Generation of Retargeted, Armed, and Reporter-Expressing Oncolytic Viruses. Viruses. 2018;10:Jun 307.
  • Mazzacurati L, Marzulli M, Reinhart B, et al. Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV. Mol Ther. 2015 Jan;23(1):99–107.
  • Kennedy EM, Farkaly T, Grzesik P, et al. Design of an Interferon-Resistant Oncolytic HSV-1 Incorporating Redundant Safety Modalities for Improved Tolerability. Mol Ther Oncolytics. 2020 Sep 25;18:476–490.
  • Meurette O, Mehlen P. Notch Signaling in the Tumor Microenvironment. Cancer Cell. 2018 Oct 8;34(4):536–548.
  • Otani Y, Yoo JY, Chao S, et al. Oncolytic HSV-Infected Glioma Cells Activate NOTCH in Adjacent Tumor Cells Sensitizing Tumors to Gamma Secretase Inhibition. Clin Cancer Res. 2020 May 15;26(10):2381–2392.
  • Otani Y, Yoo JY, Lewis CT, et al. NOTCH-Induced MDSC Recruitment after oHSV Virotherapy in CNS Cancer Models Modulates Antitumor Immunotherapy. Clin Cancer Res. 2022 Apr 1;28(7):1460–1473.
  • Long GV, Stroyakovskiy D, Gogas H, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386(9992):444–451.
  • de Gooijer MC, Zhang P, Weijer R, et al. The impact of P-glycoprotein and breast cancer resistance protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors. Int J Cancer. 2018 Jan 15;142(2):381–391.
  • Yoo JY, Swanner J, Otani Y, et al. Oncolytic HSV therapy increases trametinib access to brain tumors and sensitizes them in vivo. Neuro Oncol. 2019 Sep 6;21(9):1131–1140.
  • Hong B, Muili K, Bolyard C, et al. Suppression of HMGB1 Released in the Glioblastoma Tumor Microenvironment Reduces Tumoral Edema. Mol Ther Oncolytics. 2019 Mar 29;12:93–102.
  • Xiao J, Liang J, Fan J, et al. CDK4/6 Inhibition Enhances Oncolytic Virus Efficacy by Potentiating Tumor-Selective Cell Killing and T-cell Activation in Refractory Glioblastoma. Cancer Res. 2022 Sep 16;82(18):3359–3374.
  • Vorobyev PO, Kochetkov DV, Chumakov PM, et al. 2-Deoxyglucose, an Inhibitor of Glycolysis, Enhances the Oncolytic Effect of Coxsackievirus. Cancers (Basel). 2022 Nov 15;14:22
  • Zwernik SD, Adams BH, Raymond DA, et al. AXL receptor is required for Zika virus strain MR-766 infection in human glioblastoma cell lines. Mol Ther Oncolytics. 2021 Dec 17;23:447–457.
  • Zhu Z, Mesci P, Bernatchez JA, et al. Zika Virus Targets Glioblastoma Stem Cells through a SOX2-Integrin alphavbeta5 Axis. Cell Stem Cell. 2020 Feb 6;26(2):187–204 e10.
  • Sen A, Prager BC, Zhong C, et al. Leveraging Allele-Specific Expression for Therapeutic Response Gene Discovery in Glioblastoma. Cancer Res. 2022 Feb 1;82(3):377–390.
  • Nair S, Mazzoccoli L, Jash A, et al. Zika virus oncolytic activity requires CD8+ T cells and is boosted by immune checkpoint blockade. JCI Insight. 2021 Jan 11;6:1.
  • Chen L, Zhou C, Chen Q, et al. Oncolytic Zika virus promotes intratumoral T cell infiltration and improves immunotherapy efficacy in glioblastoma. Mol Ther Oncolytics. 2022 Mar;17(24):522–534.
  • Bulstrode H, Girdler GC, Gracia T, et al. Myeloid cell interferon secretion restricts Zika flavivirus infection of developing and malignant human neural progenitor cells. Neuron. 2022;110(23):3936–3951.e10.
  • Ochiai H, Campbell SA, Archer GE, et al. Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus. Clin Cancer Res. 2006 Feb 15;12(4):1349–1354.
  • Kaid C, Madi R, Astray R, et al. Safety, Tumor Reduction, and Clinical Impact of Zika Virus Injection in Dogs with Advanced-Stage Brain Tumors. Mol Ther. 2020 May 6;28(5):1276–1286.
  • Kang KD, Bernstock JD, Totsch SK, et al. Safety and efficacy of intraventricular immunovirotherapy with oncolytic HSV-1 for CNS cancers. Clin Cancer Res. 2022;28(24):5419–5430.
  • Spencer D, Yu D, Morshed RA, et al. Pharmacologic modulation of nasal epithelium augments neural stem cell targeting of glioblastoma. Theranostics. 2019;9(7):2071–2083.
  • Martuza RL, Malick A, Markert JM, et al. Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science. 1991 May 10;252(5007):854–856.
  • Miller KE, Cassady KA, Roth JC, et al. Immune Activity and Response Differences of Oncolytic Viral Therapy in Recurrent Glioblastoma: Gene Expression Analyses of a Phase IB Study. Clin Cancer Res. 2022 Feb 1;28(3):498–506.
  • Stavrakaki E, Dirven CMF, Lamfers MLM. Personalizing Oncolytic Virotherapy for Glioblastoma: In Search of Biomarkers for Response. Cancers (Basel). 2021 Feb;13(4):4.
  • Kim M, Kim S, Park YW, et al. Sex as a prognostic factor in adult-type diffuse gliomas: an integrated clinical and molecular analysis according to the 2021 WHO classification. J Neurooncol. 2022 Sep;159(3):695–703.
  • Shireman JM, Ammanuel S, Eickhoff JC, et al. Sexual dimorphism of the immune system predicts clinical outcomes in glioblastoma immunotherapy: A systematic review and meta-analysis. Neurooncol Adv. 2022 Jan-Dec;4(1):vdac082.
  • Bayik D, Zhou Y, Park C, et al. Myeloid-Derived Suppressor Cell Subsets Drive Glioblastoma Growth in a Sex-Specific Manner. Cancer Discov. 2020 Aug;10(8):1210–1225.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.