Virotherapy: From single agents to combinatorial treatments

Malfitano, Anna Maria; Somma, Sarah Di; Iannuzzi, Carmelina Antonella; Pentimalli, Francesca; Portella, Giuseppe

doi:10.1016/j.bcp.2020.113986

Cited by 34 publications

(38 citation statements)

References 95 publications

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“…Nonetheless, the combination of immunotherapy and in particular virotherapy with cytotoxic chemotherapy is heavily discussed [50]. Advantages of this combination were found to be highly depending on the dosing scheme and time interval [51,52].…”

Section: Discussionmentioning

confidence: 99%

Oncolytic vaccinia virus GLV-1h68 exhibits profound antitumoral activities in cell lines originating from neuroendocrine neoplasms

et al. 2020

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Background: Oncolytic virotherapy is an upcoming treatment option for many tumor entities. But so far, a first oncolytic virus only was approved for advanced stages of malignant melanomas. Neuroendocrine tumors (NETs) constitute a heterogenous group of tumors arising from the neuroendocrine system at diverse anatomic sites. Due to often slow growth rates and (in most cases) endocrine non-functionality, NETs are often detected only in a progressed metastatic situation, where therapy options are still severely limited. So far, immunotherapies and especially immunovirotherapies are not established as novel treatment modalities for NETs. Methods: In this immunovirotherapy study, pancreatic NET (BON-1, QGP-1), lung NET (H727, UMC-11), as well as neuroendocrine carcinoma (NEC) cell lines (HROC-57, NEC-DUE1) were employed. The well characterized genetically engineered vaccinia virus GLV-1 h68, which has already been investigated in various clinical trials, was chosen as virotherapeutical treatment modality. Results: Profound oncolytic efficiencies were found for NET/NEC tumor cells. Besides, NET/NEC tumor cell bound expression of GLV-1 h68-encoded marker genes was observed also. Furthermore, a highly efficient production of viral progenies was detected by sequential virus quantifications. Moreover, the mTOR inhibitor everolimus, licensed for treatment of metastatic NETs, was not found to interfere with GLV-1 h68 replication, making a combinatorial treatment of both feasible. Conclusions: In summary, the oncolytic vaccinia virus GLV-1 h68 was found to exhibit promising antitumoral activities, replication capacities and a potential for future combinatorial approaches in cell lines originating from neuroendocrine neoplasms. Based on these preliminary findings, virotherapeutic effects now have to be further evaluated in animal models for treatment of Neuroendocrine neoplasms (NENs).

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Section: Discussionmentioning

confidence: 99%

Oncolytic vaccinia virus GLV-1h68 exhibits profound antitumoral activities in cell lines originating from neuroendocrine neoplasms

et al. 2020

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“…Additionally, TAMs are mainly responsible for resistance to well-known antitumor treatments like chemotherapy and radiotherapy, indeed they limit the efficacy of immunotherapy, i.e., anti-PD1 treatment [3][4][5]. However, depending on the tumor type and treatment adopted it might be possible to identify novel approaches, i.e., combinatory therapies also taking advantage of more recent treatments as those based on the use of oncolytic viruses (OV) [6][7][8][9]. In this review, we will highlight TAMs as therapeutic target and their modulation by anticancer therapies.…”

Section: Introductionmentioning

confidence: 99%

Tumor-Associated Macrophage Status in Cancer Treatment

Malfitano

Pisanti

Napolitano

et al. 2020

Cancers

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Tumor-associated macrophages (TAMs) represent the most abundant innate immune cells in tumors. TAMs, exhibiting anti-inflammatory phenotype, are key players in cancer progression, metastasis and resistance to therapy. A high TAM infiltration is generally associated with poor prognosis, but macrophages are highly plastic cells that can adopt either proinflammatory/antitumor or anti-inflammatory/protumor features in response to tumor microenvironment stimuli. In the context of cancer therapy, many anticancer therapeutics, apart from their direct effect on tumor cells, display different effects on TAM activation status and density. In this review, we aim to evaluate the indirect effects of anticancer therapies in the modulation of TAM phenotypes and pro/antitumor activity.

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“…A variety of human and animal viruses have been tested for their application as oncolytic viruses (OVs) including herpes viruses, pox viruses, the Edmonton strain of Measles virus and, most frequently, adenoviruses since they have few side effects and their genomes are easily manipulated. The ability of viruses to target cancer cells arises from their exploitation of the aberrant signaling pathways and the generally poor antiviral response produced by cancer cells [126].…”

Section: What Can We Learn From Approved Viral Therapies; Bacterial Vmentioning

confidence: 99%

“…Contact between cancer cells and virus triggers a stress response involving reactive oxygen species (ROS) and release of Damage-Associated Molecular Patterns (DAMPs), also initiating an immune response [128]. Although OVs lyse a variety of cell types in vitro, the outcomes of their clinical use are enhanced by combination with other treatments, such as immune therapy [129] or general or targeted chemotherapy [130] for a wide range of cancer types [126].…”

Section: What Can We Learn From Approved Viral Therapies; Bacterial Vmentioning

confidence: 99%

“…Oncolytic viruses (OVs) have been transformed from the object of laboratory studies [126] to full scale clinical trials with the acceptance of three OVs for full clinical use [126]. A non-pathogenic ECHO virus has been registered for use in several Eastern European countries, an attenuated adenovirus has been registered for use in China and a modified herpes virus (HSV-1) was approved by the FDA and EMA in 2015 and is now used routinely for certain melanomas [126].…”

Section: What Can We Learn From Approved Viral Therapies; Bacterial Vmentioning

confidence: 99%

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Viruses of protozoan parasites and viral therapy: Is the time now right?

Barrow

Dujardin

Fasel

et al. 2020

Virol J

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Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases.

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Virotherapy: From single agents to combinatorial treatments

Cited by 34 publications

References 95 publications

Oncolytic vaccinia virus GLV-1h68 exhibits profound antitumoral activities in cell lines originating from neuroendocrine neoplasms

Oncolytic vaccinia virus GLV-1h68 exhibits profound antitumoral activities in cell lines originating from neuroendocrine neoplasms

Tumor-Associated Macrophage Status in Cancer Treatment

Viruses of protozoan parasites and viral therapy: Is the time now right?

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