Oncolytic Viruses for Malignant Glioma: On the Verge of Success?

Overview

Journal Viruses

Publisher MDPI

Specialty Microbiology

Date 2021 Aug 10

PMID 34372501

Citations 27

Authors

Yogesh R Suryawanshi

Autumn J Schulze

Affiliations

Soon will be listed here.

Abstract

Glioblastoma is one of the most difficult tumor types to treat with conventional therapy options like tumor debulking and chemo- and radiotherapy. Immunotherapeutic agents like oncolytic viruses, immune checkpoint inhibitors, and chimeric antigen receptor T cells have revolutionized cancer therapy, but their success in glioblastoma remains limited and further optimization of immunotherapies is needed. Several oncolytic viruses have demonstrated the ability to infect tumors and trigger anti-tumor immune responses in malignant glioma patients. Leading the pack, oncolytic herpesvirus, first in its class, awaits an approval for treating malignant glioma from MHLW, the federal authority of Japan. Nevertheless, some major hurdles like the blood-brain barrier, the immunosuppressive tumor microenvironment, and tumor heterogeneity can engender suboptimal efficacy in malignant glioma. In this review, we discuss the current status of malignant glioma therapies with a focus on oncolytic viruses in clinical trials. Furthermore, we discuss the obstacles faced by oncolytic viruses in malignant glioma patients and strategies that are being used to overcome these limitations to (1) optimize delivery of oncolytic viruses beyond the blood-brain barrier; (2) trigger inflammatory immune responses in and around tumors; and (3) use multimodal therapies in combination to tackle tumor heterogeneity, with an end goal of optimizing the therapeutic outcome of oncolytic virotherapy.

Citing Articles

Human Melanoma and Glioblastoma Cells Express Cathepsins Supporting Reovirus Moscow Strain Infection.

Ammour Y, Nikolaeva E, Sagimbaeva O, Shamsutdinov P, Astapenko A, Zhelaeva Y Viruses. 2025; 16(12.

PMID: 39772250 PMC: 11680368. DOI: 10.3390/v16121944.

Adipose-Derived Stem Cells as Carrier of Pro-Apoptotic Oncolytic Myxoma Virus: To Cross the Blood-Brain Barrier and Treat Murine Glioma.

Jazowiecka-Rakus J, Pogoda-Mieszczak K, Rahman M, McFadden G, Sochanik A Int J Mol Sci. 2024; 25(20).

PMID: 39457007 PMC: 11508294. DOI: 10.3390/ijms252011225.

Research progress and challenges of the PD-1/PD-L1 axis in gliomas.

Jiacheng D, Jiayue C, Ying G, Shaohua W, Wenhui L, Xinyu H Cell Biosci. 2024; 14(1):123.

PMID: 39334448 PMC: 11437992. DOI: 10.1186/s13578-024-01305-6.

CAR expression in invasive breast carcinoma and its effect on adenovirus transduction efficiency.

Phung A, Shah J, Dong T, Reid T, Larson C, Sanchez A Breast Cancer Res. 2024; 26(1):131.

PMID: 39256827 PMC: 11389499. DOI: 10.1186/s13058-024-01880-z.

Microbiota and glioma: a new perspective from association to clinical translation.

Wang W, Ou Z, Huang X, Wang J, Li Q, Wen M Gut Microbes. 2024; 16(1):2394166.

PMID: 39185670 PMC: 11352717. DOI: 10.1080/19490976.2024.2394166.

References

Sharma P, Hu-Lieskovan S, Wargo J, Ribas A . Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017; 168(4):707-723. PMC: 5391692. DOI: 10.1016/j.cell.2017.01.017. View

Rampling R, Cruickshank G, Papanastassiou V, Nicoll J, Hadley D, Brennan D . Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther. 2000; 7(10):859-66. DOI: 10.1038/sj.gt.3301184. View

Denton N, Chen C, Scott T, Cripe T . Tumor-Associated Macrophages in Oncolytic Virotherapy: Friend or Foe?. Biomedicines. 2017; 4(3). PMC: 5344259. DOI: 10.3390/biomedicines4030013. View

Vignali D, Collison L, Workman C . How regulatory T cells work. Nat Rev Immunol. 2008; 8(7):523-32. PMC: 2665249. DOI: 10.1038/nri2343. View

Russell S, Peng K, Bell J . Oncolytic virotherapy. Nat Biotechnol. 2012; 30(7):658-70. PMC: 3888062. DOI: 10.1038/nbt.2287. View

Sminia P, Westerman B . Blood-brain barrier crossing and breakthroughs in glioblastoma therapy. Br J Clin Pharmacol. 2016; 81(6):1018-20. PMC: 4876176. DOI: 10.1111/bcp.12881. View

Todo T, Martuza R, Rabkin S, Johnson P . Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing. Proc Natl Acad Sci U S A. 2001; 98(11):6396-401. PMC: 33479. DOI: 10.1073/pnas.101136398. View

Yong R, Shinojima N, Fueyo J, Gumin J, Vecil G, Marini F . Human bone marrow-derived mesenchymal stem cells for intravascular delivery of oncolytic adenovirus Delta24-RGD to human gliomas. Cancer Res. 2009; 69(23):8932-40. PMC: 2789204. DOI: 10.1158/0008-5472.CAN-08-3873. View

Ochiai H, Campbell S, Archer G, Chewning T, Dragunsky E, Ivanov A . Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus. Clin Cancer Res. 2006; 12(4):1349-54. DOI: 10.1158/1078-0432.CCR-05-1595. View

10.

Zhang W, Fulci G, Wakimoto H, Cheema T, Buhrman J, Jeyaretna D . Combination of oncolytic herpes simplex viruses armed with angiostatin and IL-12 enhances antitumor efficacy in human glioblastoma models. Neoplasia. 2013; 15(6):591-9. PMC: 3664991. DOI: 10.1593/neo.13158. View

11.

Khasraw M, Walsh K, Heimberger A, Ashley D . What is the Burden of Proof for Tumor Mutational Burden in gliomas?. Neuro Oncol. 2020; . PMC: 7849945. DOI: 10.1093/neuonc/noaa256. View

12.

Chiocca E, Abbed K, Tatter S, Louis D, Hochberg F, Barker 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. 2004; 10(5):958-66. DOI: 10.1016/j.ymthe.2004.07.021. View

13.

Freeman A, Zakay-Rones Z, Gomori J, Linetsky E, Rasooly L, Greenbaum E . Phase I/II trial of intravenous NDV-HUJ oncolytic virus in recurrent glioblastoma multiforme. Mol Ther. 2005; 13(1):221-8. DOI: 10.1016/j.ymthe.2005.08.016. View

14.

Grill J, van Beusechem V, van der Valk P, Dirven C, Leonhart A, Pherai D . Combined targeting of adenoviruses to integrins and epidermal growth factor receptors increases gene transfer into primary glioma cells and spheroids. Clin Cancer Res. 2001; 7(3):641-50. View

15.

Cohen M, Shen Y, Keegan P, Pazdur R . FDA drug approval summary: bevacizumab (Avastin) as treatment of recurrent glioblastoma multiforme. Oncologist. 2009; 14(11):1131-8. DOI: 10.1634/theoncologist.2009-0121. View

16.

Ruiz A, Hadac E, Nace R, Russell S . MicroRNA-Detargeted Mengovirus for Oncolytic Virotherapy. J Virol. 2016; 90(8):4078-4092. PMC: 4810567. DOI: 10.1128/JVI.02810-15. View

17.

Qazi M, Vora P, Venugopal C, Sidhu S, Moffat J, Swanton C . Intratumoral heterogeneity: pathways to treatment resistance and relapse in human glioblastoma. Ann Oncol. 2017; 28(7):1448-1456. DOI: 10.1093/annonc/mdx169. View

18.

Foloppe J, Kempf J, Futin N, Kintz J, Cordier P, Pichon C . The Enhanced Tumor Specificity of TG6002, an Armed Oncolytic Vaccinia Virus Deleted in Two Genes Involved in Nucleotide Metabolism. Mol Ther Oncolytics. 2019; 14:1-14. PMC: 6461584. DOI: 10.1016/j.omto.2019.03.005. View

19.

Ferguson M, Lemoine N, Wang Y . Systemic delivery of oncolytic viruses: hopes and hurdles. Adv Virol. 2012; 2012:805629. PMC: 3287020. DOI: 10.1155/2012/805629. View

20.

Thakkar J, Dolecek T, Horbinski C, Ostrom Q, Lightner D, Barnholtz-Sloan J . Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev. 2014; 23(10):1985-96. PMC: 4185005. DOI: 10.1158/1055-9965.EPI-14-0275. View