Adenovirus‐mediated Interferon‐γ Gene Therapy Induced Human Pancreatic Carcinoma Capan‐2 Cell Apoptosis <i>In Vitro</i> and <i>In Vivo</i>

Xie, Fa Jun; Zhao, Peng; Liu, Fei Ye; Nie, Xi; Zhu, Ying; Yu, Xin; Zheng, Qiu; Mao, Wei; Lü, Hong; Hong, Wei; Huang, Wenlin

doi:10.1002/ar.22661

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…Since IFN-γ can promote anti-tumorigenic effects through the activation of natural killer cell surveillance 1 2 3 4 , it is thought to be a prognostic factor for cancer therapy 5 6 7 8 . IFN-γ is also known as an anti-osteoclastogenic cytokine by its degradation of TRAF6, which results in the subsequent inhibition of RANKL signaling in osteoclasts 9 .…”

Section: Discussionmentioning

confidence: 99%

“…Interferon gamma (IFN-γ) is a cytokine that exerts an anti-tumor effect through the activation of natural killer cell surveillance 1 2 3 4 . Moreover, IFN-γ has been proposed as a prognostic factor in cancer therapy 5 6 7 8 . In addition to its anti-tumor functions, IFN-γ also exerts an anti-osteoclastogenic effect by inducing degradation of tumor necrosis factor receptor-associated factor 6 (TRAF6), resulting in the inhibition of receptor activator of nuclear factor (NF)-kappa B ligand (RANKL) signaling 9 .…”

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confidence: 99%

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A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

Kanzaki

Shinohara

Suzuki

et al. 2016

Sci Rep

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Interferon-gamma (IFN-γ) is a pleiotropic cytokine that exerts anti-tumor and anti-osteoclastogenic effects. Although transcriptional and post-transcriptional regulation of IFN-γ is well understood, subsequent modifications of secreted IFN-γ are not fully elucidated. Previous research indicates that some cancer cells escape immune surveillance and metastasize into bone tissue by inducing osteoclastic bone resorption. Peptidases of the a-disintegrin and metalloproteinase (ADAM) family are implicated in cancer cell proliferation and tumor progression. We hypothesized that the ADAM enzymes expressed by cancer cells degrades IFN-γ and attenuates IFN-γ-mediated anti-tumorigenic and anti-osteoclastogenic effects. Recombinant ADAM17 degraded IFN-γ into small fragments. The addition of ADAM17 to the culture supernatant of stimulated mouse splenocytes decreased IFN-γ concentration. However, ADAM17 inhibition in the stimulated mouse T-cells prevented IFN-γ degradation. ADAM17-expressing human breast cancer cell lines MCF-7 and MDA-MB-453 also degraded recombinant IFN-γ, but this was attenuated by ADAM17 inhibition. Degraded IFN-γ lost the functionality including the inhibititory effect on osteoclastogenesis. This is the first study to demonstrate the extracellular proteolytic degradation of IFN-γ by ADAM17. These results suggest that ADAM17-mediated degradation of IFN-γ may block the anti-tumorigenic and anti-osteoclastogenic effects of IFN-γ. ADAM17 inhibition may be useful for the treatment of attenuated cancer immune surveillance and/or bone metastases.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

Kanzaki

Shinohara

Suzuki

et al. 2016

Sci Rep

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“…Interestingly, treating cancer with Ad-IFNα resulted in higher IFNα concentration in tumors than in systemic circulation ( Ohashi et al, 2005 ), and promoted regression of non-treated distant tumors as well, also inducing T-cells and natural killer cells recruitment to tumor site ( Hara et al, 2007 ). IFNβ in an oncolytic adenovirus improved treatment ( He et al, 2008 ; Park et al, 2010 ) and adenovirus expressing IFNγ showed low systemic toxicity ( Xie et al, 2013 ; Zhao et al, 2007 ).…”

Section: Adenovirus In Cancer Gene Therapymentioning

confidence: 99%

The use of adenoviral vectors in gene therapy and vaccine approaches

et al. 2022

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Adenovirus was first identified in the 1950s and since then this pathogenic group of viruses has been explored and transformed into a genetic transfer vehicle. Modification or deletion of few genes are necessary to transform it into a conditionally or non-replicative vector, creating a versatile tool capable of transducing different tissues and inducing high levels of transgene expression. In the early years of vector development, the application in monogenic diseases faced several hurdles, including short-term gene expression and even a fatality. On the other hand, an adenoviral delivery strategy for treatment of cancer was the first approved gene therapy product. There is an increasing interest in expressing transgenes with therapeutic potential targeting the cancer hallmarks, inhibiting metastasis, inducing cancer cell death or modulating the immune system to attack the tumor cells. Replicative adenovirus as vaccines may be even older and date to a few years of its discovery, application of non-replicative adenovirus for vaccination against different microorganisms has been investigated, but only recently, it demonstrated its full potential being one of the leading vaccination tools for COVID-19. This is not a new vector nor a new technology, but the result of decades of careful and intense work in this field.

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“…[8][9][10] Therefore the concept of delivering the necessary dose of treatment directly to the target tissue has been investigated with (a) gene therapy, (b) immunotherapy and (c) chemotherapy or combinations of the above methods. [11][12][13][14][15][16][17] The following methods for intratumoral treatment have been used: (a) brachytherapy, (b) photodynamic therapy, (c) thermal and non-thermal ablative therapies, (d) chemotherapy, and (e) gene therapy. 16,[18][19][20] Gene therapy has been used for lung cancer to sensitize cells to radiotherapy and chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector–p53

et al. 2013

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Lung cancer still remains to be challenged by novel treatment modalities. Novel locally targeted routes of administration are a methodology to enhance treatment and reduce side effects. Intratumoral gene therapy is a method for local treatment and could be used either in early-stage lung cancer before surgery or at advanced stages as palliative care. Novel non-viral vectors are also in demand for efficient gene transfection to target local cancer tissue and at the same time protect the normal tissue. In the current study, C57BL/6 mice were divided into three groups: (a) control, (b) intravenous and (c) intatumoral gene therapy. The novel 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector (Ryujyu Science Corporation) was conjugated with plasmid pSicop53 from the company Addgene for the first time. The aim of the study was to evaluate the safety and efficacy of targeted gene therapy in a Lewis lung cancer model. Indeed, although the pharmacokinetics of the different administration modalities differs, the intratumoral administration presented increased survival and decreased distant metastasis. Intratumoral gene therapy could be considered as an efficient local therapy for lung cancer.

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Adenovirus‐mediated Interferon‐γ Gene Therapy Induced Human Pancreatic Carcinoma Capan‐2 Cell Apoptosis In Vitro and In Vivo

Cited by 9 publications

References 20 publications

A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

A-Disintegrin and Metalloproteinase (ADAM) 17 Enzymatically Degrades Interferon-gamma

The use of adenoviral vectors in gene therapy and vaccine approaches

Intratumoral gene therapy versus intravenous gene therapy for distant metastasis control with 2-Diethylaminoethyl-Dextran Methyl Methacrylate Copolymer Non-Viral Vector–p53

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