Virotherapy of Neuroendocrine Tumors

Essand, Magnus

doi:10.1159/000336084

Cited by 12 publications

(14 citation statements)

References 100 publications

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“…In addition, TAAs released from the dying tumour cells can be captured by the DCs. In order to enhance this effect even further, strategies have been developed to arm oncolytic viruses with immunestimulatory genes (Essand 2013). A phase I trial (NCT00314925) is being planned to study the side effects and the best dose of Seneca Valley virus-001 for the treatment of patients with advanced solid tumours with neuroendocrine features.…”

Section: Tumour-promoting Inflammationmentioning

confidence: 99%

Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment

Walenkamp¹,

Crespo²,

Maya³

et al. 2014

Endocrine-Related Cancer

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In the past few years, there have been advances in the treatment of neuroendocrine tumours (NETs) and improvements in our understanding of NET biology. However, the benefits to patients have been relatively modest and much remains yet to be done. The 'Hallmarks of Cancer', as defined by Hanahan and Weinberg, provide a conceptual framework for understanding the aberrations that underlie tumourigenesis and to help identify potential targets for therapy. In this study, our objective is to review the major molecular characteristics of NETs, based on the recently modified 'Hallmarks of Cancer', and highlight areas that require further research.

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Section: Tumour-promoting Inflammationmentioning

confidence: 99%

Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment

Walenkamp¹,

Crespo²,

Maya³

et al. 2014

Endocrine-Related Cancer

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“…For a recent review on virus-based therapy of NETs readers are referred to Essand [46] . Our group has systematically developed a recombinant oncolytic adenovirus to treat NETs, which is about to enter a clinical trial for GEP-NET patients with liver metastases.…”

Section: Oncolytic Viruses As Immunotherapymentioning

confidence: 99%

“…The adenovirus E1A gene is directly responsible for virus replication; therefore, this genetic alteration blocks virus replication in all cells that are not of neuroendocrine origin. Furthermore, to reduce potential liver toxicity we have introduced target sequences for liver-specific microRNAs in the virus genome, thereby minimizing the activity of the virus in healthy liver cells [46] .…”

Section: Oncolytic Viruses As Immunotherapymentioning

confidence: 99%

Other Novel Therapies: Biomarkers, microRNAs and microRNA Inhibitors, DNA Methylation, Epigenetics, Immunotherapy and Virotherapy

Giandomenico

Thirlwell²,

Essand³

2015

Neuroendocrine Tumors: A Multidisciplinary Approach

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Neuroendocrine tumors (NETs) consist of heterogeneous neoplasms. The neuroendocrine cells of the human body are confined to certain organs, such as the thyroid, pancreas and adrenals, or they are dispersed throughout the body in the respiratory tract and in the intestinal mucosa. The cells belong to the diffuse endocrine cell system, share a neuroendocrine phenotype, and accumulate precursor molecules which are then processed into hormones, peptides or amines. The tightly controlled release on stimulation is either to the blood stream or adjacent cells or neurons. Neuroendocrine cells regulate various processes in the human body, such as gastrointestinal secretion, blood pressure and response to stress. NETs present a wide spectrum of malignant diseases from rather benign to very malignant and lethal variants. NETs may occur in any organ, but are mainly detected in the gastroenteropancreatic system and in the lungs. The understanding of NET biology and treatments has changed dramatically during the last decade. Today, the main problems that clinicians and translational scientists face in overcoming these malignancies relate to various aspects within the molecular pathogenesis of NETs. This chapter focuses on the importance of novel biomarkers: microRNA and microRNA inhibitors; DNA methylation and epigenetics, and immunotherapy and virotherapy to develop novel treatments for NETs.

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“…Only very few approaches using oncolytic virotherapy in NEN treatment have been described so far [7][8][9][10]: oncolytic viruses (OV) are engineered to speci cally target tumor cells, to produce enormous amounts of viral progeny within and thus to damage them harshly, resulting in signi cant rates of tumor cell lysis, i.e. oncolysis.…”

Section: Introductionmentioning

confidence: 99%

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

Kloker

Berchtold

Smirnow

et al. 2020

Preprint

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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-1h68, 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-1h68-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-1h68 replication, making a combinatorial treatment of both feasible. Conclusions: In summary, the oncolytic vaccinia virus GLV-1h68 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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Virotherapy of Neuroendocrine Tumors

Cited by 12 publications

References 100 publications

Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment

Hallmarks of gastrointestinal neuroendocrine tumours: implications for treatment

Other Novel Therapies: Biomarkers, microRNAs and microRNA Inhibitors, DNA Methylation, Epigenetics, Immunotherapy and Virotherapy

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

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