The Emerging Field of Oncolytic Virus-based Cancer Immunotherapy

Overview

Journal Trends Cancer

Publisher Cell Press

Specialty Oncology

Date 2022 Nov 19

PMID 36402738

Authors

Rui Ma

Zhenlong Li

E Antonio Chiocca

Michael A Caligiuri

Jianhua Yu

Affiliations

Soon will be listed here.

Abstract

Oncolytic viruses (OVs) provide novel and promising therapeutic options for patients with cancers resistant to traditional therapies. Natural or genetically modified OVs are multifaceted tumor killers. They directly lyse tumor cells while sparing normal cells, and indirectly potentiate antitumor immunity by releasing antigens and activating inflammatory responses in the tumor microenvironment. However, some limitations, such as limited penetration of OVs into tumors, short persistence, and the host antiviral immune response, are impeding the broad translation of oncolytic virotherapy into the clinic. If these challenges can be overcome, combination therapies, such as OVs plus immune checkpoint blockade (ICB), chimeric antigen receptor (CAR) T cells, or CAR natural killer (NK) cells, may provide powerful therapeutic platforms in the clinic.

Citing Articles

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References

Lipatova A, Soboleva A, Gorshkov V, Bubis J, Solovyeva E, Krasnov G . Multi-Omics Analysis of Glioblastoma Cells' Sensitivity to Oncolytic Viruses. Cancers (Basel). 2021; 13(21). PMC: 8582528. DOI: 10.3390/cancers13215268. View

Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka R, Michielin O . Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017; 170(6):1109-1119.e10. PMC: 8034392. DOI: 10.1016/j.cell.2017.08.027. View

Jochems C, Tucker J, Tsang K, Madan R, Dahut W, Liewehr D . A combination trial of vaccine plus ipilimumab in metastatic castration-resistant prostate cancer patients: immune correlates. Cancer Immunol Immunother. 2014; 63(4):407-18. PMC: 6314199. DOI: 10.1007/s00262-014-1524-0. View

Chan W, Kang S, Youssef Y, Glankler E, Barrett E, Carter A . A CS1-NKG2D Bispecific Antibody Collectively Activates Cytolytic Immune Cells against Multiple Myeloma. Cancer Immunol Res. 2018; 6(7):776-787. PMC: 6030494. DOI: 10.1158/2326-6066.CIR-17-0649. View

Poh A . First Oncolytic Viral Therapy for Melanoma. Cancer Discov. 2015; 6(1):6. DOI: 10.1158/2159-8290.CD-NB2015-158. View

Pecora A, Rizvi N, Cohen G, Meropol N, Sterman D, Marshall J . Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol. 2002; 20(9):2251-66. DOI: 10.1200/JCO.2002.08.042. View

Chen L, Chen H, Ye J, Ge Y, Wang H, Dai E . Intratumoral expression of interleukin 23 variants using oncolytic vaccinia virus elicit potent antitumor effects on multiple tumor models via tumor microenvironment modulation. Theranostics. 2021; 11(14):6668-6681. PMC: 8171085. DOI: 10.7150/thno.56494. View

Friedman G, Johnston J, Bag A, Bernstock J, Li R, Aban I . Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas. N Engl J Med. 2021; 384(17):1613-1622. PMC: 8284840. DOI: 10.1056/NEJMoa2024947. View

Sathaiah M, Thirunavukkarasu P, OMalley M, Kavanagh M, Ravindranathan R, Austin F . Oncolytic poxvirus armed with Fas ligand leads to induction of cellular Fas receptor and selective viral replication in FasR-negative cancer. Cancer Gene Ther. 2011; 19(3):192-201. PMC: 3288301. DOI: 10.1038/cgt.2011.77. View

10.

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

11.

Sugawara K, Iwai M, Yajima S, Tanaka M, Yanagihara K, Seto Y . Efficacy of a Third-Generation Oncolytic Herpes Virus G47Δ in Advanced Stage Models of Human Gastric Cancer. Mol Ther Oncolytics. 2020; 17:205-215. PMC: 7178322. DOI: 10.1016/j.omto.2020.03.022. View

12.

Todo T, Ito H, Ino Y, Ohtsu H, Ota Y, Shibahara J . Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial. Nat Med. 2022; 28(8):1630-1639. PMC: 9388376. DOI: 10.1038/s41591-022-01897-x. View

13.

Cervera-Carrascon V, Quixabeira D, Havunen R, Santos J, Kutvonen E, Clubb J . Comparison of Clinically Relevant Oncolytic Virus Platforms for Enhancing T Cell Therapy of Solid Tumors. Mol Ther Oncolytics. 2020; 17:47-60. PMC: 7163046. DOI: 10.1016/j.omto.2020.03.003. View

14.

Otani Y, Yoo J, Chao S, Liu J, Jaime-Ramirez A, Lee T . Oncolytic HSV-Infected Glioma Cells Activate NOTCH in Adjacent Tumor Cells Sensitizing Tumors to Gamma Secretase Inhibition. Clin Cancer Res. 2020; 26(10):2381-2392. PMC: 7325527. DOI: 10.1158/1078-0432.CCR-19-3420. View

15.

Hodgins J, Khan S, Park M, Auer R, Ardolino M . Killers 2.0: NK cell therapies at the forefront of cancer control. J Clin Invest. 2019; 129(9):3499-3510. PMC: 6715409. DOI: 10.1172/JCI129338. View

16.

Han J, Chen X, Chu J, Xu B, Meisen W, Chen L . TGFβ Treatment Enhances Glioblastoma Virotherapy by Inhibiting the Innate Immune Response. Cancer Res. 2015; 75(24):5273-82. PMC: 4681611. DOI: 10.1158/0008-5472.CAN-15-0894. View

17.

Hingorani M, Spitzweg C, Vassaux G, Newbold K, Melcher A, Pandha H . The biology of the sodium iodide symporter and its potential for targeted gene delivery. Curr Cancer Drug Targets. 2010; 10(2):242-67. PMC: 3916908. DOI: 10.2174/156800910791054194. View

18.

Tahtinen S, Gronberg-Vaha-Koskela S, Lumen D, Merisalo-Soikkeli M, Siurala M, Airaksinen A . Adenovirus Improves the Efficacy of Adoptive T-cell Therapy by Recruiting Immune Cells to and Promoting Their Activity at the Tumor. Cancer Immunol Res. 2015; 3(8):915-25. DOI: 10.1158/2326-6066.CIR-14-0220-T. View

19.

Chiocca E . Oncolytic viruses. Nat Rev Cancer. 2002; 2(12):938-50. DOI: 10.1038/nrc948. View

20.

Zhang H, Xie W, Zhang Y, Dong X, Liu C, Yi J . Oncolytic adenoviruses synergistically enhance anti-PD-L1 and anti-CTLA-4 immunotherapy by modulating the tumour microenvironment in a 4T1 orthotopic mouse model. Cancer Gene Ther. 2021; 29(5):456-465. PMC: 9113929. DOI: 10.1038/s41417-021-00389-3. View