Production of pharmaceutical glycoproteins, such as therapeutic antibodies and cytokines, in plants has many advantages in safety and reduced costs. However, plant-made glycoproteins have N-glycans with plant-specific sugar residues (core β-1,2-xylose and α-1,3-fucose) and a Lewis a (Le(a)) epitope, Galβ(1-3)[Fucα(1-4)]GlcNAc. Because it is likely that these sugar residues and glycan structures are immunogenic, many attempts have been made to delete them. Previously, we reported the simultaneous deletion of the plant-specific core α-1,3-fucose and α-1,4-fucose residues in Le(a) epitopes by repressing the GDP-D-mannose 4,6-dehydratase (GMD) gene, which is associated with GDP-L-fucose biosynthesis, in Nicotiana benthamiana plants (rGMD plants, renamed to ΔGMD plants) (Matsuo and Matsumura, Plant Biotechnol. J., 9, 264-281, 2011). In the present study, we generated a core β-1,2-xylose residue-repressed transgenic N. benthamiana plant by co-suppression of β-1,2-xylosyltransferase (ΔXylT plant). By crossing ΔGMD and ΔXylT plants, we successfully generated plants in which plant-specific sugar residues were repressed (ΔGMDΔXylT plants). The proportion of N-glycans with deleted plant-specific sugar residues found in total soluble protein from ΔGMDΔXylT plants increased by 82.41%. Recombinant mouse granulocyte/macrophage-colony stimulating factor (mGM-CSF) and human monoclonal immunoglobulin G (hIgG) harboring N-glycans with deleted plant-specific sugar residues were successfully produced in ΔGMDΔXylT plants. Simultaneous repression of the GMD and XylT genes in N. benthamiana is thus very useful for deleting plant-specific sugar residues.

2012-09-01·Journal of Immunotherapy4区 · 医学

Differential Immunologic and MicroRNA Effects of 2 Dosing Regimens of Recombinant Human Granulocyte/Macrophage Colony Stimulating Factor

4区 · 医学

Article

作者: Garcia, Jorge ; Aldrich, Wayne ; Triozzi, Pierre L. ; Elson, Paul ; Achberger, Susan ; Dreicer, Robert

Recombinant human (rh) granulocyte/macrophage colony stimulating factor (GM-CSF) has demonstrated antitumor immunologic activity in prostate and other cancers. Dosing has been empiric, and biomarkers of effect have not been established. Eight patients with biochemical relapse of prostate cancer were randomized into group A, in which they received rhGM-CSF at 250 µg/m days 1-14 of a 28-day cycle, and 8 were randomized into group B, in which they received 250 µg 3 times a week continuously. Blood dendritic cell (DC), immune suppressor cell, cytokine, and microRNA (miR) levels were examined using flow cytometric, enzyme-linked immunosorbent, and/or polymerase chain reaction-based assays. Group A had greater increases in myeloid DC and in granulocyte and monocytes. In croup B, plasmacytoid DC decreased. In group A, DC production of interleukin-12 relative to interleukin-10 decreased; this ratio increased in group B. Increases in myeloid-derived suppressor cells were observed in both the groups with increases greater in group A. Increases in regulatory T cells and in serum tumor necrosis and vascular endothelial growth factors were only observed in group A. Serum miR-155 decreased in group A. An increase in serum miR-223 and a decrease in miR-125b and miR-146a were observed in group B. The dosing of rhGM-CSF influences immune and miR effects. More DC activation and fewer myeloid-derived suppressor and regulatory T cells are observed when administered at lower doses intermittently and continuously compared with when administered at higher doses daily and cyclically. Serum levels of miRs are potentially useful biomarkers of these effects.

2012-09-01·Burns3区 · 医学

Recombinant human granulocyte-macrophage colony-stimulating factor hydrogel promotes healing of deep partial thickness burn wounds

3区 · 医学

Article

作者: Xi Peng ; Jian Chen ; Hong Yan

OBJECTIVETo assess the effects of recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF) hydrogel on the healing of deep partial thickness burn wounds.METHODSNinety three wounds of 65 burn patients who suffered from a deep partial thickness burn of <5% TBSA and could not heal over 3 weeks were included in this study. The patients were randomly assigned to use rhGM-CSF hydrogel (GC group, n=32) or hydrogel without rhGM-CSF (control group, n=33). rhGM-CSF hydrogel or hydrogel without rhGM-CSF was topically applied to the wounds, the dressing was changed once a day. Wound healing time and percentage, wound discharge, periwound inflammation, the positive wound swabs culture count, and adverse drug reactions were observed and compared between two groups.RESULTSHealing time was 12.2 ± 5.0 days after the application of rhGM-CSF hydrogel. This was significantly shorter than that of control wounds (15.5 ± 4.7 days). Healing percentage at 14 days in the rhGM-CSF-treated wounds was 97.5 ± 7.7%, which was markedly higher than the control (85.9 ± 6.8%). At 3, 6, 12, 14 day, the GC group was significantly superior to the control group with respect to the score of periwound inflammation, wound purulence and discharge. The positive wound swabs culture count of the GC group on the 7th and 14th day post-treatment was 14 and 4, respectively, which was significantly lower than the control.CONCLUSIONrhGM-CSF hydrogel promotes the healing process of deep partial thickness burns effectively. No adverse reaction of the drug was observed during the study.

100 项与重组人粒细胞/巨噬细胞集落刺激因子 (广州白云山医药集团) 相关的药物交易

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适应症	国家/地区	公司	日期
白细胞减少	中国	广州白云山拜迪生物医药有限公司	2005-10-10
骨髓增生异常综合征	中国	广州白云山拜迪生物医药有限公司	2005-10-10