Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics
Top Cited Papers
Open Access
- 9 January 2019
- journal article
- review article
- Published by BMJ in Journal for ImmunoTherapy of Cancer
- Vol. 7 (1), 6
- https://doi.org/10.1186/s40425-018-0495-7
Abstract
Cancer vaccines and oncolytic immunotherapy are promising treatment strategies with potential to provide greater clinical benefit to patients with advanced-stage cancer. In particular, recombinant vaccinia viruses (VV) hold great promise as interventional agents. In this article, we first summarize the current understanding of virus biology and viral genes involved in host-virus interactions to further improve the utility of these agents in therapeutic applications. We then discuss recent findings from basic and clinical studies using VV as cancer vaccines and oncolytic immunotherapies. Despite encouraging results gleaned from translational studies in animal models, clinical trials implementing VV vectors alone as cancer vaccines have yielded largely disappointing results. However, the combination of VV vaccines with alternate forms of standard therapies has resulted in superior clinical efficacy. For instance, combination regimens using TG4010 (MVA-MUC1-IL2) with first-line chemotherapy in advanced-stage non-small cell lung cancer or combining PANVAC with docetaxel in the setting of metastatic breast cancer have clearly provided enhanced clinical benefits to patients. Another novel cancer vaccine approach is to stimulate anti-tumor immunity via STING activation in Batf3-dependent dendritic cells (DC) through the use of replication-attenuated VV vectors. Oncolytic VVs have now been engineered for improved safety and superior therapeutic efficacy by arming them with immune-stimulatory genes or pro-apoptotic molecules to facilitate tumor immunogenic cell death, leading to enhanced DC-mediated cross-priming of T cells recognizing tumor antigens, including neoantigens. Encouraging translational and early phase clinical results with Pexa-Vec have matured into an ongoing global phase III trial for patients with hepatocellular carcinoma. Combinatorial approaches, most notably those using immune checkpoint blockade, have produced exciting pre-clinical results and warrant the development of innovative clinical studies. Finally, we discuss major hurdles that remain in the field and offer some perspectives regarding the development of next generation VV vectors for use as cancer therapeutics.Funding Information
- National Institutes of Health (1R01CA155925)
- National Cancer Institute (1R01CA168912)
This publication has 199 references indexed in Scilit:
- Vaccinia Virus Induces Programmed Necrosis in Ovarian Cancer CellsMolecular Therapy, 2013
- Vaccinia virus F1L protein promotes virulence by inhibiting inflammasome activationProceedings of the National Academy of Sciences, 2013
- The Oncolytic Poxvirus JX-594 Selectively Replicates in and Destroys Cancer Cells Driven by Genetic Pathways Commonly Activated in CancersMolecular Therapy, 2012
- Therapeutic Cancer Vaccines: Current Status and Moving ForwardJNCI Journal of the National Cancer Institute, 2012
- Intranodal Immunization With a Vaccinia Virus Encoding Multiple Antigenic Epitopes and Costimulatory Molecules in Metastatic MelanomaMolecular Therapy, 2010
- Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancerCancer Immunology, Immunotherapy, 2009
- Comparison of intravenous versus intraperitoneal administration of oncolytic herpes simplex virus 1 for peritoneal carcinomatosis in miceCancer Gene Therapy, 2008
- Chemical targeting of the innate antiviral response by histone deacetylase inhibitors renders refractory cancers sensitive to viral oncolysisProceedings of the National Academy of Sciences of the United States of America, 2008
- A Phase II Study of Tg4010 (Mva-Muc1-Il2) in Association with Chemotherapy in Patients with Stage III/IV Non-small Cell Lung CancerJournal of Thoracic Oncology, 2008
- Colocalization of Transcription and Translation within Cytoplasmic Poxvirus Factories Coordinates Viral Expression and Subjugates Host FunctionsCell Host & Microbe, 2007