Genetically Engineered Vaccinia Viruses As Agents for Cancer Treatment, Imaging, and Transgene Delivery

Haddad, Dana

doi:10.3389/fonc.2017.00096

Cited by 66 publications

(51 citation statements)

References 112 publications

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“…It is worth noting that combination of NIS-mediated imaging with ionizing radiation (e.g. 131 I) may have a synergistic effect in cancer therapy, which can be attributed to viral replication increase in response to upregulation of some DNA repairing pathways or also α decay particles produced by 131 I (0.2-2.4 mm in path length) [48,49].…”

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confidence: 99%

Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

et al. 2020

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Compared with conventional cancer treatments, the main advantage of oncolytic virotherapy is its tumor-selective replication followed by the destruction of malignant cells without damaging healthy cells. Accordingly, this kind of biological therapy can potentially be used as a promising approach in the field of cancer management. Given the failure of traditional monitoring strategies (such as immunohistochemical analysis (in providing sufficient safety and efficacy necessary for virotherapy and continual pharmacologic monitoring to track pharmacokinetics in real-time, the development of alternative strategies for ongoing monitoring of oncolytic treatment in a live animal model seems inevitable. Three-dimensional molecular imaging methods have recently been considered as an attractive approach to overcome the limitations of oncolytic therapy. These noninvasive visualization systems provide real-time follow-up of viral progression within the cancer tissue by the ability of engineered oncolytic viruses (OVs) to encode reporter transgenes based on recombinant technology. Human sodium/iodide symporter (hNIS) is considered as one of the most prevalent nuclear imaging reporter transgenes that provides precise information regarding the kinetics of gene expression, viral biodistribution, toxicity, and therapeutic outcomes using the accumulation of radiotracers at the site of transgene expression. Here, we provide an overview of pre-clinical and clinical applications of hNIS-based molecular imaging to evaluate virotherapy efficacy. Moreover, we describe different types of reporter genes and their potency in the clinical trials.

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confidence: 99%

Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

et al. 2020

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“…Understanding the distribution and replication status of OVs in vivo helps in assessing the efficacy and safety of OVs [163]. OV replication can be monitored by incorporating them with reporter genes, such GFP and Rluc (usually used for optical imaging), NIS, and human norepinephrine transporter (NET) (usually used for deep tissue imaging) [164]. GFP insertion is widely used in OVT, and multiple OVs expressing GFP have been developed, such as MV-GFP (MV) [165], JX-GFP (VACV) [104], and rFMW/GFP (NDV) [166].…”

Section: Monitoring Ov Replicationmentioning

confidence: 99%

“…With the expression of GFP, fluorescence imaging can be used to directly observe the localization of OVs. However, monitoring OVs or tumors in deep tissues via GFP and Rluc is difficult, whereas NIS or NET can be used to monitor OV replication in deep tissues [164]. NIS is a membrane ion channel that mediates iodine transport.…”

Section: Monitoring Ov Replicationmentioning

confidence: 99%

Development of oncolytic virotherapy: from genetic modification to combination therapy

et al. 2020

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Oncolytic virotherapy (OVT) is a novel form of immunotherapy using natural or genetically modified viruses to selectively replicate in and kill malignant cells. Many genetically modified oncolytic viruses (OVs) with enhanced tumor targeting, antitumor efficacy, and safety have been generated, and some of which have been assessed in clinical trials. Combining OVT with other immunotherapies can remarkably enhance the antitumor efficacy. In this work, we review the use of wild-type viruses in OVT and the strategies for OV genetic modification. We also review and discuss the combinations of OVT with other immunotherapies.

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“…Successful examples include a recombinant VACV expressing the rabies virus glycoprotein (V-RG) that has been used in Europe and North America against sylvatic rabies [59], and a VACV expressing rinderpest virus glycoproteins provided long-term sterilizing immunity in cattle [60]. Currently, a number of clinical trials are underway for animal and human vaccines, immunotherapies, and oncolytic therapies based on replication-competent VACV vectors [61,62]. However, the potential for severe adverse reactions is a concern, especially in individuals with predisposing conditions.…”

Section: Plos Onementioning

confidence: 99%

Replication-inducible vaccinia virus vectors with enhanced safety in vivo

et al. 2020

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Vaccinia virus (VACV) has been used extensively as the vaccine against smallpox and as a viral vector for the development of recombinant vaccines and cancer therapies. Replicationcompetent, non-attenuated VACVs induce strong, long-lived humoral and cell-mediated immune responses and can be effective oncolytic vectors. However, complications from uncontrolled VACV replication in vaccinees and their close contacts can be severe, particularly in individuals with predisposing conditions. In an effort to develop replication-competent VACV vectors with improved safety, we placed VACV late genes encoding core or virion morphogenesis proteins under the control of tet operon elements to regulate their expression with tetracycline antibiotics. These replication-inducible VACVs would only express the selected genes in the presence of tetracyclines. VACVs inducibly expressing the A3L or A6L genes replicated indistinguishably from wild-type VACV in the presence of tetracyclines, whereas there was no evidence of replication in the absence of antibiotics. These outcomes were reflected in mice, where the VACV inducibly expressing the A6L gene caused weight loss and mortality equivalent to wild-type VACV in the presence of tetracyclines. In the absence of tetracyclines, mice were protected from weight loss and mortality, and viral replication was not detected. These findings indicate that replication-inducible VACVs based on the conditional expression of the A3L or A6L genes can be used for the development of safer, next-generation live VACV vectors and vaccines. The design allows for administration of replication-inducible VACV in the absence of tetracyclines (as a replication-defective vector) or in the presence of tetracyclines (as a replication-competent vector) with enhanced safety.

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Genetically Engineered Vaccinia Viruses As Agents for Cancer Treatment, Imaging, and Transgene Delivery

Cited by 66 publications

References 112 publications

Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

Virotheranostics, a double-barreled viral gun pointed toward cancer; ready to shoot?

Development of oncolytic virotherapy: from genetic modification to combination therapy

Replication-inducible vaccinia virus vectors with enhanced safety in vivo

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