Improved therapeutic efficacy of mammalian expressed-recombinant interferon gamma against ovarian cancer cells

Razaghi, Ali; Villacrés, Carina; Jung, Vincent; Mashkour, Narges; Butler, Michael; Owens, Leigh; Heimann, Kirsten

doi:10.1016/j.yexcr.2017.08.014

Cited by 17 publications

(11 citation statements)

References 40 publications

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“…The different eukaryotic expression systems producing specific N-glycan would also affect therapeutic applications. For example, mammalian-expressed hIFNγ with complex-type glycosylation exhibited higher levels of biological activity against cancer cells compared to its deglycosylated form (Razaghi et al, 2017b). However, the heterogeneous N-glycan side chains of plantproduced hIFNγ have not yet been completely identified to date.…”

Section: Post-translational Modification During Protein Transportatiomentioning

confidence: 99%

Fusion of a Novel Native Signal Peptide Enhanced the Secretion and Solubility of Bioactive Human Interferon Gamma Glycoproteins in Nicotiana benthamiana Using the Bamboo Mosaic Virus-Based Expression System

Jiang

Hsu

et al. 2020

Front. Plant Sci.

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Plant viruses may serve as expression vectors for the efficient production of pharmaceutical proteins in plants. However, the downstream processing and post-translational modifications of the target proteins remain the major challenges. We have previously developed an expression system derived from Bamboo mosaic virus (BaMV), designated pKB19, and demonstrated its applicability for the production of human mature interferon gamma (mIFNγ) in Nicotiana benthamiana . In this study, we aimed to enhance the yields of soluble and secreted mIFNγ through the incorporation of various plant-derived signal peptides. Furthermore, we analyzed the glycosylation patterns and the biological activity of the mIFNγ expressed by the improved pKB19 expression system in N. benthamiana . The results revealed that the fusion of a native N. benthamiana extensin secretory signal (SS Ext ) to the N-terminal of mIFNγ (designated SS Ext mIFNγ) led to the highest accumulation level of protein in intracellular (IC) or apoplast washing fluid (AWF) fractions of N. benthamiana leaf tissues. The addition of 10 units of ‘Ser-Pro’ motifs of hydroxyproline-O-glycosylated peptides (HypGPs) at the C-terminal end of SS Ext mIFNγ (designated SS Ext mIFNγ(SP) 10 ) increased the solubility to nearly 2.7- and 1.5-fold higher than those of mIFNγ and SS Ext mIFNγ, respectively. The purified soluble SS Ext mIFNγ(SP) 10 protein was glycosylated with abundant complex-type N-glycan attached to residues N 56 and N 128 , and exhibited biological activity against Sindbis virus and Influenza virus replication in human cell culture systems. In addition, suspension cell cultures were established from transgenic N. benthamiana , which produced secreted SS Ext mIFNγ(SP) 10 protein feasible for downstream processing. These results demonstrate the applicability of the BaMV-based vector systems as a useful alternative for the production of therapeutic proteins, through the incorporation of appropriate fusion tags.

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Section: Post-translational Modification During Protein Transportatiomentioning

confidence: 99%

Fusion of a Novel Native Signal Peptide Enhanced the Secretion and Solubility of Bioactive Human Interferon Gamma Glycoproteins in Nicotiana benthamiana Using the Bamboo Mosaic Virus-Based Expression System

Jiang

Hsu

et al. 2020

Front. Plant Sci.

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“…In the study by Liu S. et al 51 it was observed that specific expression of interferon-γ induced by synergistic activation mediator-derived (SAM) systems activates innate immunity and inhibits tumorigenesis. In the study by Razaghi A. et al 52 improved therapeutic efficacy of mammalian expressed-recombinant interferon gamma against ovarian cancer cells was observed. In the study by Li Z. et al 53 it was observed that anti-VEGFR-interferon-α2 regulates the tumor microenvironment and exhibits potent antitumor efficacy against colorectal cancer.…”

Section: Interferon-γmentioning

confidence: 99%

Interferon-γ and Colorectal Cancer: an up-to date

et al. 2018

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Colorectal cancer still remains the third cause of cancer death among cancer patients. Early diagnosis is crucial and they can be either endoscopic or with blood biomarkers. Endoscopic methods consist of gastroscopy and colonoscopy, however; in recent years, endoscopic ultrasound is being used. The microenvironment is very important for the successful delivery of the treatment. Several proteins and hormones play a crucial role in the efficiency of the treatment. In the current mini review we will focus on interferon-γ.

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“…The main objective of this research was to cluster the patients using their data expression of 20 genes which, based on the clinical literature, are the most effective genes in prediction, diagnosis and treatment of the ovarian cancer (Windbichler et al, 2000;Sers et al, 2002;Marth et al, 2004;Manrique et al, 2011;Bankaitis and Fingleton, 2015;Berinstein et al, 2015;Shang et al, 2015;Comisso et al, 2017;Razaghi et al, 2017;Yokoyama et al, 2017). Since one cannot exactly determine which method is always the most appropriate clustering method for a data type (Ciaramella and Staiano, 2019), comparison of different methods on a data set is of great importance.…”

Section: Evaluation Of Twenty Genes In Prognosis Of Patients With Ovarian Cancer Using Four Different Clustering Methodsmentioning

confidence: 99%

Evaluation of Twenty Genes in Prognosis of Patients with Ovarian Cancer Using Four Different Clustering Methods

Pourahmad

Foroozani

Nourelahi

et al. 2021

Asian Pac J Cancer Prev

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Background: Comparison of gene expression algorithms may be beneficial for obtaining disease pattern or grouping patients based on the gene expression profile. The current study aimed to investigate whether the knowledge within these data is able to group the ovarian cancer patients with similar disease pattern. Methods: Four different clustering methods were applied on 20 genes expression data of 37 women with ovarian cancer. All selected genes in this study had prominent roles in the control of the activity of the immune system, as well as the chemotaxis, angiogenesis, apoptosis, and etc. Comparison of different clustering methods such as K-means, Hierarchical, Density-Based Spatial Clustering of Applications with Noise (DBSCAN) and Expectation-Maximization (EM) algorithm was the other aim of the present study. In addition, the percentage of correct prediction, Robustness-Performance Trade-off (RPT), and Silhouette criteria were used to evaluate the performance of clustering methods. Results: Six out of 20 genes (IFN-γ, Foxp3, IL-4, BCL-2, Oct4 and survivin) selected by the Laplacian score showed key roles in the development of ovarian cancer and their prognostic values were clinically and statistically confirmed. The results indicated proper capability of the expression pattern of these genes in grouping the patients with similar prognosis, i.e. patients alive after 5 years or dead (62.12%). Conclusion: The results revealed the better performance for k-means and hierarchical clustering methods, and confirmed the fact that by using the expression profile of these genes, patients with similar behavior can be grouped in the same cluster with acceptable accuracy level. Certainly, the useful information from these data may contribute to the prediction of prognosis in ovarian cancer patients along with other features of patients.

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Improved therapeutic efficacy of mammalian expressed-recombinant interferon gamma against ovarian cancer cells

Cited by 17 publications

References 40 publications

Fusion of a Novel Native Signal Peptide Enhanced the Secretion and Solubility of Bioactive Human Interferon Gamma Glycoproteins in Nicotiana benthamiana Using the Bamboo Mosaic Virus-Based Expression System

Fusion of a Novel Native Signal Peptide Enhanced the Secretion and Solubility of Bioactive Human Interferon Gamma Glycoproteins in Nicotiana benthamiana Using the Bamboo Mosaic Virus-Based Expression System

Interferon-γ and Colorectal Cancer: an up-to date

Evaluation of Twenty Genes in Prognosis of Patients with Ovarian Cancer Using Four Different Clustering Methods

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