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Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer
Abstract
Viruses have been engineered for cancer therapy in a variety of ways. Approaches include non-replicating gene therapy vectors, cancer vaccines and oncolytic viruses, but the clinical efficacy of these approaches has been limited by multiple factors. However, a new therapeutic class of oncolytic poxviruses has recently been developed that combines targeted and armed approaches for treating cancer. Initial preclinical and clinical results show that products from this therapeutic class can systemically target cancers in a highly selective and potent fashion using a multi-pronged mechanism of action.
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“Moreover, oncolytic viruses can be armed with vectors that encode for pro-inflammatory or anti-immunosuppressive transgenes, thereby in theory promoting both the immunogenicity of the tumour cells and intratumoral inflammation.128”
From Current and emerging concepts for systemic treatment of metastatic colorectal cancer (2025) · cites this paper as [128]
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Oncolytic virotherapy for pancreatic cancer
Wennier, S. T., Li, S., & McFadden, G. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411001876 · Cited by 29
Huang, T., Wang, H., Chen, N. G., Frentzen, A., Minev, B., & Szalay, A. A. (2015) · Molecular Therapy — Oncolytics · doi:10.1038/mto.2015.3 · Cited by 30
Oncolytic viruses and pancreatic cancer
Hamidi-Sofiani, V., Rakhshi, R., Moradi, N., Zeynali, P., Nakhaie, M., & Behboudi, E. (2022) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2022.100563 · Cited by 30
Double‐deleted vaccinia virus in virotherapy for refractory and metastatic pediatric solid tumors
Lun, X., Ruan, Y., Jayanthan, A., Liu, D. J., Singh, A., Trippett, T. M., Bell, J. C., Forsyth, P. A., Johnston, R. N., & Narendran, A. (2013) · Molecular Oncology · doi:10.1016/j.molonc.2013.05.004 · Cited by 28
“Although vaccinia virus infects most of the tumors studied, the molecular mechanisms that govern tumor selectivity are yet to be identified. vvDD depends on the availability of viral transformation genes present in the tumor cells for their replication (Kirn and Thorne, 2009).”
BackgroundInhibitors of C5 complement enhance vaccinia virus oncolysis
Magge, D. R., Guo, Z. S., O’Malley, M. E., Francis, L., Ravindranathan, R., & Bartlett, D. L. (2013) · Cancer Gene Therapy · doi:10.1038/cgt.2013.26 · Cited by 28
Chen, N. G., Yu, Y., Zhang, Q., & Szalay, A. A. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-164 · Cited by 28
“It is believed that an unarmed oncolytic virus destroys tumors through one, or most likely, a combination of the following mechanisms: 1) by direct viral oncolysis of tumor cells; 2) by destruction of the tumor vasculature [4,28]; and 3) by induction of host antitumoral immune responses [29,30].”
BackgroundOncolytic viral therapy: targeting cancer stem cells
Gillespie, G. Y., Roth, J. C., Friedman, G. K., & Smith, T. (2014) · Oncolytic Virotherapy · doi:10.2147/ov.s52749 · Cited by 27
“Additionally, larger viruses can be armed to express immunestimulating transgenes to recruit an influx of immune effector cells to further augment their therapeutic effect.(57,58) After infection of tumor cells, oncolytic virus replication generates progeny that are released by cytolysis to infect nearby tumor cells,…”
Viral delivery for gene therapy against cell movement in cancer
Wu, T.-L., & Zhou, D. (2011) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.05.005 · Cited by 27
Jiang, T., Yang, T., Chen, Y., Miao, Y., Xu, Y., Jiang, H., Yang, M., & Mao, C. (2022) · Theranostics · doi:10.7150/thno.70719 · Cited by 31
“But they are abundant in tumors such as poliovirus [128], herpes simplex virus (HSV) [50], adenovirus [52], and vaccinia virus [129].”
BackgroundMejías‐Pérez, E., Carreño‐Fuentes, L., & Estéban, M. (2017) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2017.12.002 · Cited by 27
“With the release of tumor antigens by cell lysis, these features generate protective antitumor immunity.(13) A number of oncolytic poxviruses have been developed and are under study in preclinical and clinical trials;(14) the most advanced candidates include JX-594 (Wyeth strain)(4) and GL-ONC1 (Liverpool strain).”
BackgroundZhang, S., Wang, W., Cai, W., Jiang, K., & Yuan, Z. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-427 · Cited by 26
“The MV enters the cells through the interaction of the H-glycoprotein with the MV receptors, CD150 (signaling lymphocyte-activation molecule, SLAM) and CD46 [41-43].”
BackgroundOncolytic viruses as a promising therapeutic strategy for hematological malignancies
Yang, C., Hua, N., Xie, S., Wu, Y., Zhu, L., Wang, S., & Tong, X. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111573 · Cited by 26
Pan‐Hammarström, Q., Huang, Y., Chen, L., Gu, J., & Zhou, X. (2014) · Human Cell · doi:10.1007/s13577-014-0093-z · Cited by 26
“The engineered vaccinia virus is an effective and highly selective vehicle for the delivery of exogenous functional genes into tumor cells [31, 32].”
BackgroundHughes, J., Wang, P., Alusi, G., Shi, H., Chu, Y., Wang, J., Bhakta, V., McNeish, I. A., McCart, A., Lemoine, N. R., et al. (2015) · Gene Therapy · doi:10.1038/gt.2015.13 · Cited by 26
Baker, J. L., & Ward, B. M. (2013) · Journal of Virological Methods · doi:10.1016/j.jviromet.2013.10.026 · Cited by 26
Definition of an Enhanced Immune Cell Therapy in Mice That Can Target Stem-Like Lymphoma Cells
Contag, C. H., Sikorski, R. P., Negrin, R. S., Schmidt, T. L., Fan, A. C., Bachireddy, P., Felsher, D. W., & Thorne, S. H. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2650 · Cited by 26
“Copyright © 2010 American Association for Cancer Research 3 Introduction We recently described a novel combination approach for the treatment of cancer(1), utilizing a tumor-targeting immune cell (cytokine induced killer; CIK cells)(2, 3), as a carrier vehicle to systemically deliver an oncolytic vaccinia virus (vvDD)…”
Self-citationCytolytic replication of echoviruses in colon cancer cell lines
Israelsson, S., Jonsson, N., Gullberg, M., & Lindberg, A. M. (2011) · Virology Journal · doi:10.1186/1743-422x-8-473 · Cited by 26
“Several other viruses, including poxviruses, reovirus and Newcastle disease virus have also shown promising antitumor effects in various human malignancies (reviewed in [4,8-10]).”
BackgroundHasegawa, N., Abei, M., Yokoyama, K. K., Fukuda, K., Seo, E., Kawashima, R., Nakano, Y., Yamada, T., Nakade, K., Hamada, H., et al. (2013) · International Journal of Cancer · doi:10.1002/ijc.28132 · Cited by 25
Naturally occurring, tumor-specific, therapeutic proteins
Argiris, K., Panethymitaki, C., & Tavassoli, M. (2011) · Experimental Biology and Medicine · doi:10.1258/ebm.2011.011004 · Cited by 25
Recent advances in oncolytic virus design
Hernández-Alcoceba, R. (2011) · Clinical & Translational Oncology · doi:10.1007/s12094-011-0647-4 · Cited by 25
“Trials of a VV expressing GM-CSF (JX-594; Green Cross Corp/Jennerex Inc) revealed objective responses in patients with melanoma and liver cancer, some of them in non-injected lesions and in the presence of neutralising antibodies (reviewed in [ 75 ]).”
BackgroundMadlambayan, G. J., Bartee, E., Kim, M., Rahman, M. M., Meacham, A. M., Scott, E. W., McFadden, G., & Cogle, C. R. (2012) · Leukemia Research · doi:10.1016/j.leukres.2012.01.020 · Cited by 25
“Significant progress has been made in developing many of these viruses as antineoplastic agents and several are currently in clinical trials [3, 4], including a genetically modified adenovirus, H101, which was recently approved by China’s State Food and Drug Administration for the treatment of head and neck cancer.”
BackgroundEffective Oncolytic Vaccinia Therapy for Human Sarcomas
He, S., Li, P., Chen, C., Bakst, R. L., Chernichenko, N., Yu, Y., Chen, N. G., Szalay, A. A., Yu, Z., Fong, Y., et al. (2011) · Journal of Surgical Research · doi:10.1016/j.jss.2011.11.1030 · Cited by 25
“Immune responses induced by vaccinia can provide beneficial anti-tumor effects [17, 18].”
BackgroundTrail armed oncolytic poxvirus suppresses lung cancer cell by inducing apoptosis
Hu, J., Wang, H., Gu, J., Liu, X., & Zhou, X. (2018) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmy096 · Cited by 25
Oncolytic virotherapy evolved into the fourth generation as tumor immunotherapy
Wang, X., Shen, Y., Wan, X., Hu, X., Cai, W.-Q., Wu, Z., Xin, Q., Liu, X., Gui, J., Xin, H.-Y., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04360-8 · Cited by 25
Current and Future Management Strategies for Relapsed or Progressive Hepatoblastoma
Venkatramani, R., Furman, W. L., Fuchs, J., Warmann, S. W., & Malogolowkin, M. H. (2012) · Pediatric Drugs · doi:10.2165/11597740-000000000-00000 · Cited by 24
Poxviruses as Gene Therapy Vectors: Generating Poxviral Vectors Expressing Therapeutic Transgenes
Conrad, S. J., & Liu, J. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9065-8_11 · Cited by 22
Pseudomonas aeruginosa ExoT induces G1 cell cycle arrest in melanoma cells
Mohamed, M. F., Wood, S. J., Roy, R., Reiser, J., Kuzel, T. M., & Shafikhani, S. H. (2021) · Cellular Microbiology · doi:10.1111/cmi.13339 · Cited by 22
“…p.f.u.) (Breitbach et al., 2011; Park et al., 2008); intravenous stability and the ability to spread to distant tissues (Vanderplasschen, Mathew, Hollinshead, Sim, & Smith, 1998); and preferential accumulation in solid tumours where neovasculature shows increased permeability (Kirn & Thorne, 2009).”
BackgroundAlmansour, N. M., Pirogova, E., Coloe, P. J., Ćosić, I., & Istivan, T. S. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.98 · Cited by 22
Oncolytic virus and immunogenic cell death in cancer therapy
Cao, G., Ding, C., Dai, J., & Qiu, X. (2025) · Tumour Virus Research · doi:10.1016/j.tvr.2025.200333 · Cited by 22
“VACV is an enveloped double-stranded DNA (dsDNA) virus, a member of the Poxviridae family (Orthopoxvirus genus), that replicates exclusively in the cytoplasm and is a naturally occurring oncolytic virus [327].”
Tumor Tropism of DNA Viruses for Oncolytic Virotherapy
Enow, J. A., Sheikh, H. I., & Rahman, M. M. (2023) · Viruses · doi:10.3390/v15112262 · Cited by 23
“Another EEV-associated protein, B5R, responsible for viral morphogenesis, trafficking, and dissemination and involved in the non-specific targeting of healthy and tumor cells, was engineered to enable tumor-specific replication, evading virus neutralization while retaining oncolytic activity [17,18].”
Background
Metadata
- Authors
- Kirn, D. H., & Thorne, S. H.
- ORCID
- Kirn, David H.
- Venue
- Nature Reviews Cancer
- Published
- 2009-01
- Volume
- 9
- Issue
- 1
- Pages
- 64-71
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- OpenAlex
- W2079647238
- Cited by
- 402
- References
- 134
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 19 · 2023: 14 · 2022: 16 · 2021: 16 · 2020: 20 · 2019: 14 · 2018: 16 · 2017: 24 · 2016: 25 · 2015: 29 · 2014: 29 · 2013: 49 · 2012: 36
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature reviews. Cancer (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Virology › Poxvirus research and outbreaks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Keywords
- vaccinia virus, cancer gene therapy, cancer vaccines, viral vectors
- MeSH terms
- Animals, Forecasting, Humans, Immunity, Cellular, Inflammation, Neoplasm Metastasis, Neoplasms, Poxviridae, Vaccinia virus, Virus Replication, Gene Expression Regulation, Viral, Cancer Vaccines, Oncolytic Virotherapy, Oncolytic Viruses, Mice, Host-Pathogen Interactions
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