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Glucose-methanol-based fed-batch fermentation for the production of recombinant human interferon gamma (rhIFN-γ) and evaluation of its antitumor potential.

Glucose-methanol-based fed-batch fermentation for the production of recombinant human interferon gamma (rhIFN-γ) and evaluation of its antitumor potential.

Authors :
Prabhu AA
Kumar JP
Mandal BB
Veeranki VD
Source :
Biotechnology and applied biochemistry [Biotechnol Appl Biochem] 2020 Nov; Vol. 67 (6), pp. 973-982. Date of Electronic Publication: 2020 Feb 05.
Publication Year :
2020

Abstract

Squamous cell carcinoma (SCC) is nonmelanoma skin cancer, which is very common in patients having T-cell immunosuppressant drugs. Anticancerous agents such as cytokines showed effective response on SCC. Human interferon-gamma (hIFN-γ), a type II cytokines, are having potent antiproliferative and immunomodulatory effects. In the current study, the fed-batch cultivation of recombinant Pichia pastoris was carried out, and its effect on cell biomass production, recombinant human interferon-gamma (rhIFN-γ) production, and the overflow metabolites was estimated. P. pastoris GS115 strain coexpressed with 6-phosphogluconolactonase (SOL3) and ribulose-phosphate 3-epimerase (RPE1) gene (GS115/rhIFN-γ/SR) resulted in 60 mg L <superscript>-1</superscript> of rhIFN-γ production, which was twofold higher as compared with the production from GS115/rhIFN-γ strain. The antiproliferative potential of rhIFN-γ was examined on the human squamous carcinoma (A431) cell lines. Cells treated with 80 ng mL <superscript>-1</superscript> of rhIFN-γ exhibited 50% growth inhibition by enhancing the production of intracellular reactive oxygen species levels and disrupting membrane integrity. Our findings highlight a state of art process development strategy for the high-level production of rhIFN-γ and its potential application as a therapeutic drug in SCC therapy.<br /> (© 2019 International Union of Biochemistry and Molecular Biology, Inc.)

Details

Language :
English
ISSN :
1470-8744
Volume :
67
Issue :
6
Database :
MEDLINE
Journal :
Biotechnology and applied biochemistry
Publication Type :
Academic Journal
Accession number :
31811672
Full Text :
https://doi.org/10.1002/bab.1868