Viral genes as oncolytic agents for cancer therapy

Gupta, Shishir Kumar; Gandham, Ravi Kumar; Sahoo, Aditya Prasad; Tiwari, Ashok Kumar

doi:10.1007/s00018-014-1782-1

Cited by 13 publications

(9 citation statements)

References 205 publications

(257 reference statements)

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“…Due to the nature of their location, approaches are also limited. We undertook the OV approach, since it represents an exciting biological approach to cancer therapy with a distinct mechanism of action when compared with conventional cancer therapeutics in that OVs selectively replicate and ultimately lyse tumor cells [ 8 , 37 ]. Kambara et al reported that the oHSV-1 mutant (rQNestin34.5), which we used in this study, was engineered by expressing ICP34.5 under the control of a synthetic nestin promoter, so it can selectively replicate in nestin positive tumors [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases

et al. 2016

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Breast cancer brain metastases (BCBMs) are common in patients with metastatic breast cancer and indicate a poor prognosis. These tumors are especially resistant to currently available treatments due to multiple factors. However, the combination of chimeric antigen receptor (CAR)-modified immune cells and oncolytic herpes simplex virus (oHSV) has not yet been explored in this context. In this study, NK-92 cells and primary NK cells were engineered to express the second generation of EGFR-CAR. The efficacies of anti-BCBMs of EGFR-CAR NK cells, oHSV-1, and their combination were tested in vitro and in a breast cancer intracranial mouse model. In vitro, compared with mock-transduced NK-92 cells or primary NK cells, EGFR-CAR-engineered NK-92 cells and primary NK cells displayed enhanced cytotoxicity and IFN-γ production when co-cultured with breast cancer cell lines MDA-MB-231, MDA-MB-468, and MCF-7. oHSV-1 alone was also capable of lysing and destroying these cells. However, a higher cytolytic effect of EGFR-CAR NK-92 cells was observed when combined with oHSV-1 compared to the monotherapies. In the mice intracranially pre-inoculated with EGFR-expressing MDA-MB-231 cells, intratumoral administration of either EGFR-CAR-transduced NK-92 cells or oHSV-1 mitigated tumor growth. Notably, the combination of EGFR-CAR NK-92 cells with oHSV-1 resulted in more efficient killing of MDA-MB-231 tumor cells and significantly longer survival of tumor-bearing mice when compared to monotherapies. These results demonstrate that regional administration of EGFR-CAR NK-92 cells combined with oHSV-1 therapy is a potentially promising strategy to treat BCBMs.

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Section: Discussionmentioning

confidence: 99%

A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases

et al. 2016

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“…To avoid the side-effects associated with using whole viruses as oncolytic agents, oncolytic viral gene therapy instead employs a single viral gene (or a combination of genes) which on ectopic expression finds and selectively destroys malignant cells. Oncolytic genes are non-toxic and biodegradable, have a large therapeutic index, have a limited pathogenicity to normal tissue, can be repeatedly administered without loss of function, do not pose serious socio-environmental hazards, escape immune system unlike complete viral particles and can be effectively targeted using peptide vehicles (like peptide nano-cages) to induce apoptosis in transformed cells ( Noteborn, 2009 ; Pavet et al, 2011 ; Backendorf and Noteborn, 2014 ; Gupta et al, 2015 ; Lezhnin et al, 2015 ).…”

Section: Viruses and Their Genes As Anti-cancer (Oncolytic) Agentsmentioning

confidence: 99%

Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems

Malla

Arora

Khan

et al. 2020

Front. Cell Dev. Biol.

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Cancer remains one of the leading causes of death worldwide in humans and animals. Conventional treatment regimens often fail to produce the desired outcome due to disturbances in cell physiology that arise during the process of transformation. Additionally, development of treatment regimens with no or minimum side-effects is one of the thrust areas of modern cancer research. Oncolytic viral gene therapy employs certain viral genes which on ectopic expression find and selectively destroy malignant cells, thereby achieving tumor cell death without harming the normal cells in the neighborhood. Apoptin, encoded by Chicken Infectious Anemia Virus’ VP3 gene, is a proline-rich protein capable of inducing apoptosis in cancer cells in a selective manner. In normal cells, the filamentous Apoptin becomes aggregated toward the cell margins, but is eventually degraded by proteasomes without harming the cells. In malignant cells, after activation by phosphorylation by a cancer cell-specific kinase whose identity is disputed, Apoptin accumulates in the nucleus, undergoes aggregation to form multimers, and prevents the dividing cancer cells from repairing their DNA lesions, thereby forcing them to undergo apoptosis. In this review, we discuss the present knowledge about the structure of Apoptin protein, elaborate on its mechanism of action, and summarize various strategies that have been used to deliver it as an anticancer drug in various cancer models.

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“…MicroRNAs provide a cost-effective, fast and efficient means for gene therapy [14,15]. Currently, the strategy for downregulating survivin to induce apoptosis shows great promise in cancer gene therapy [16]. Future endeavours should be directed to the development of a delivery system such as non-viral vectors [17,18] that could efficiently and safely introduce genes into cancer cells.…”

Section: Comparison Of the Impacts Of The Combined Mir-34a/e4orf4 Andmentioning

confidence: 99%

MicroRNA-34a and E4orf4 synergistically promote apoptosis in Hela cells

Zhang

Rao

Chen

et al. 2019

Biotechnology & Biotechnological Equipment

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RNA interference (RNAi) mediated by microRNA (miRNA) is widely utilized to induce apoptosis and further inhibit the proliferation of cancer cells. MiroRNA-34a (miR-34a) is one of the most potent apoptosis inducers by targeting survivin, which is associated with cancer initiation and progression. To further induce apoptosis and inhibit proliferation in Hela cells, the cytokine E4orf4 is included. One of the advantages of E4orf4 is that it can induce apoptosis independent of p53, which is especially useful for p53-mutant cancers. In our study, we successfully constructed a vector co-expressing miR-34a and E4orf4. The vector was transfected into Hela cells and the proliferation, metastasis and apoptosis of Hela cells were evaluated. We further compared the combined use of miR-34a and E4orf4 with pri-miR-34a in the potency of apoptosis induction. It is concluded that miR-34a and E4orf4 have a synergistic impact on Hela cell proliferation, metastasis and apoptosis, providing an efficient tool for further cervical cancer gene therapy.

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Viral genes as oncolytic agents for cancer therapy

Cited by 13 publications

References 205 publications

A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases

A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases

Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems

MicroRNA-34a and E4orf4 synergistically promote apoptosis in Hela cells

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