A pharmacokinetic study to comparatively evaluate the bioequivalence and safety of a humanized recombinant monoclonal antibody targeting human epidermal growth factor receptor-2 with the reference Herceptin in healthy Chinese subjects
Purpose: This study aimed to compare the safety, tolerability, pharmacokinetics (PK), and bioequivalence of a test humanized recombinant monoclonal antibody targeting human epidermal growth factor receptor-2 (HER-2) with the reference Herceptin®.
Materials and methods: The trial consisted of two parts (part I and part II). Part I was an open-label, sequential-cohort dose-escalation study, where 16 healthy subjects were either intravenously infused with QLHER2 (test) at single doses escalating from 0.2 to 6 mg/kg (0.2, 1, 2, 4, and 6 mg/kg) or given 4 mg/kg Herceptin (reference) for evaluating the safety, tolerability, and PK of QLHER2. Part II was a randomized, double-blind, parallel-group study to evaluate the bioequivalence of QLHER2 and Herceptin in 60 subjects.
Results: Following a 1.5-h intravenous infusion of single ascending doses of QLHER2 (1, 2, 4, or 6 mg/kg) in part I, Cmax and Tmax were 19.43-120.01 μg/mL and 68.91-157.87 h, respectively. AUC0-t and CL were 1.91-34.21 h·μg/mL and 0.54-0.12 mL/h/kg, indicating lower clearance at higher doses, with a greater than proportional increase in AUC0-t and t1/2 of 68.91-157.87 h. In part II, serum concentrations were comparable between QLHER2 and Herceptin over a 70-day sampling period, and the QLHER2/Herceptin ratios of Cmax and AUC0-t were 105.90% [90% confidence interval (CI): 95.69%-117.26%] and 95.79% (90% CI: 87.74%-106.40%), respectively.
Conclusion: The 90% CI value of Cmax and AUC0-t for QLHER2/Herceptin ratio ranged between 80.0%-125.00%, indicating that QLHER2 was bioequivalent to Herceptin. These results support further evaluation of QLHER2. Trial registration number: ChiCTR2000041577 and ChiCTR2100041802. Date of registration: 30th December, 2020 and 5th January 2021.
Recombinant Apyrase (AZD3366) Against Myocardial Reperfusion Injury
Purpose: Recombinant apyrase (AZD3366) increases adenosine production and ticagrelor inhibits adenosine reuptake. We investigated whether intravenous AZD3366 before reperfusion reduces myocardial infarct size (IS) and whether AZD3366 and ticagrelor have additive effects.
Methods: Sprague-Dawley rats underwent 30 min ischemia. At 25 min of ischemia, animals received intravenous AZD3366 or vehicle. Additional animals received intravenous CGS15943 (an adenosine receptor blocker) or intraperitoneal ticagrelor. At 24 h reperfusion, IS was assessed by triphenyltetrazolium chloride. Other rats were subjected to 30 min ischemia followed by 1 h or 24 h reperfusion. Myocardial samples were assessed for adenosine levels, RT-PCR, and immunoblotting.
Results: AZD3366 and ticagrelor reduced IS. The protective effect was blocked by CGS15943. The effect of AZD3366 + ticagrelor was significantly greater than AZD3366. One hour after infarction, myocardial adenosine levels significantly increased with AZD3366, but not with ticagrelor. In contrast, 24 h after infarction, adenosine levels were equally increased by AZD3366 and ticagrelor, and levels were higher in the AZD3366 + ticagrelor group. One hour after reperfusion, AZD3366 and ticagrelor equally attenuated the increase in interleukin-15 (an early inflammatory marker after ischemic cell death) levels, and their combined effects were additive. AZD3366, but not ticagrelor, significantly attenuated the increase in RIP1, RIP3, and P-MLKL (markers of necroptosis) 1 h after reperfusion. AZD3366, but not ticagrelor, significantly attenuated the increase in IL-6 and GSDMD-N (markers of pyroptosis) 1 h after reperfusion. At 24 h of reperfusion, both agents equally attenuated the increase in these markers, and their effects were additive.
Conclusions: AZD3366 attenuated inflammation, necrosis, necroptosis, and pyroptosis and limited IS. The effects of AZD3366 and ticagrelor were additive.
Production of recombinant β-glucocerebrosidase in wild-type and glycoengineered transgenic Nicotiana benthamiana root cultures with different N-glycan profiles
- Gaucher disease is an inherited lysosomal storage disorder caused by an insufficiency of active β-glucocerebrosidase (GCase). Exogenous recombinant GCase via enzyme replacement therapy is considered the most practical treatment for Gaucher disease. Mannose receptors mediate the efficient uptake of exogenous GCase into macrophages. Thus, terminal mannose residues on N-glycans are essential for the delivery of exogenous GCase. In this study, recombinant GCase was produced in root cultures of wild-type (WT) and glycoengineered transgenic Nicotiana benthamiana with downregulated N-acetylglucosaminyltransferase I expression.
- Root cultures of WT and glycoengineered transgenic N. benthamiana plants were successfully generated by the induction of plant hormones. Recombinant GCases produced in both root cultures possessed GCase enzyme activity. Purified GCases derived from both root cultures revealed different N-glycan profiles.
- The WT-derived GCase possessed the predominant plant-type N-glycans, which contain plant-specific sugars-linkages, specifically β1,2-xylose and α1,3-fucose residues. Notably, the mannosidic-type N-glycans with terminal mannose residues were abundant in the purified GCase derived from glycoengineered N. benthamiana root culture. This research provides a promising plant-based system for the production of recombinant GCase with terminal mannose residues on N-glycans.
Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs
Background: Porcine endogenous retroviruses (PERVs) can infect human cells and pose a risk for xenotransplantation when pig cells, tissues or organs are transplanted to human recipients. Xenotransplantation holds great promise to overcome the shortage of human donor organs after solving the problems of rejection, functionality and virus safety. We recently described the transmission of a human-tropic recombinant PERV-A/C, designated PERV-F, from peripheral blood mononuclear cells (PBMCs) of a Göttingen Minipig (GöMP) to human 293 cells (Krüger et al., in Viruses 12(1):38, 2019). The goal of this study was to characterize PERV-F in more detail and to analyze the probability of virus isolation from other animals.
Methods: The recombination site in the envelope (env) gene, the long terminal repeats (LTR), the proteins and the morphology of the recombinant PERV-F were characterized by polymerase chain reaction (PCR), sequencing, Western blot analysis, immunofluorescence, and transmissible electron microscopy. Mitogen-stimulated PBMCs from 47 additional pigs, including 17 new GöMP, were co-cultured with highly susceptible human 293 T cells, and the PERV-A/C prevalence and PERV transmission was analyzed by PCR.
Results: PERV-F, isolated from a GöMP, is an infectious human-tropic PERV-A/C virus with a novel type of recombination in the env gene. The length of the LTR of PERV-F increased after passaging on human cells. In a few minipigs, but not in German landrace pigs, PERV-A/C were found. There was no transmission of human-tropic PERV-A/C from additional 47 pigs, including 17 GöMP, to human cells.
Conclusion: These data show that human-tropic recombinant PERV-A/C proviruses can only be found in a very small number of minipigs, but not in other pigs, and that their isolation as infectious virus able to replicate on human cells is an extremely rare event, even when using highly susceptible 293 cells.
PRTN3 Protein, Human, Recombinant (203S/A, His Tag) |
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| MBS8118685-01mg | MyBiosource | 0.1mg | 450 EUR |
PRTN3 Protein, Human, Recombinant (203S/A, His Tag) |
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| MBS8118685-5x01mg | MyBiosource | 5x0.1mg | 1885 EUR |
Recombinant-SARS-CoV-2/COVID-19-NSP1 |
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| E40COV410 | EnoGene | N/A | 346.5 EUR |
Recombinant-SARS-CoV-2/COVID-19-NSP8 |
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| E40COV413 | EnoGene | N/A | 346.5 EUR |
Glypican 3 Protein, Human, Recombinant (495S/A, hFc Tag) |
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| MBS8119991-005mg | MyBiosource | 0.05mg | 275 EUR |
Glypican 3 Protein, Human, Recombinant (495S/A, hFc Tag) |
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| MBS8119991-05mg | MyBiosource | 0.5mg | 1325 EUR |
Glypican 3 Protein, Human, Recombinant (495S/A, hFc Tag) |
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| MBS8119991-5x05mg | MyBiosource | 5x0.5mg | 5810 EUR |
Glypican 3 Protein, Human, Recombinant (495S/A, mFc Tag) |
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| MBS8119992-005mg | MyBiosource | 0.05mg | 275 EUR |
Glypican 3 Protein, Human, Recombinant (495S/A, mFc Tag) |
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| MBS8119992-05mg | MyBiosource | 0.5mg | 1325 EUR |
Glypican 3 Protein, Human, Recombinant (495S/A, mFc Tag) |
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| MBS8119992-5x05mg | MyBiosource | 5x0.5mg | 5810 EUR |
Recombinant-SARS-CoV-2/COVID-19-PL-Pro |
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| E40COV408 | EnoGene | N/A | 346.5 EUR |
Recombinant-SARS-CoV-2/COVID-19-NSP10 |
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| E40COV412 | EnoGene | N/A | 346.5 EUR |
Recombinant-SARS-CoV-2(2019-nCoV)M-protein |
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| E28AB0036 | EnoGene | N/A | 400 EUR |
Recombinant-SARS-CoV-2(2019-nCoV)E-protein |
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| E28AB0037 | EnoGene | N/A | 400 EUR |
Recombinant-SARS-CoV-2(2019-nCoV)S1-Protein |
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| E28AB0026 | EnoGene | N/A | 533.33 EUR |
Recombinant-SARS-CoV-2(2019-nCoV)S1-Protein |
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| E28AB0027 | EnoGene | N/A | 400 EUR |
Recombinant-SARS-CoV-2(2019-nCoV)S2-Protein |
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| E28AB0028 | EnoGene | N/A | 400 EUR |
Recombinant 40S ribosomal protein SA (rps-0) |
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| MBS1206229-005mgBaculovirus | MyBiosource | 0.05mg(Baculovirus) | 1110 EUR |
Recombinant 40S ribosomal protein SA (rps-0) |
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| MBS1206229-005mgEColi | MyBiosource | 0.05mg(E-Coli) | 795 EUR |
Recombinant 40S ribosomal protein SA (rps-0) |
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| MBS1206229-005mgYeast | MyBiosource | 0.05mg(Yeast) | 945 EUR |
Recombinant 40S ribosomal protein SA (rps-0) |
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| MBS1206229-02mgEColi | MyBiosource | 0.2mg(E-Coli) | 1060 EUR |
Recombinant 40S ribosomal protein SA (rps-0) |
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| MBS1206229-05mgEColi | MyBiosource | 0.5mg(E-Coli) | 1130 EUR |
Recombinant 30S ribosomal protein S7 (rpsG) |
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| MBS1217414-005mgBaculovirus | MyBiosource | 0.05mg(Baculovirus) | 870 EUR |
Recombinant 30S ribosomal protein S7 (rpsG) |
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| MBS1217414-005mgEColi | MyBiosource | 0.05mg(E-Coli) | 485 EUR |
Recombinant 30S ribosomal protein S7 (rpsG) |
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| MBS1217414-005mgYeast | MyBiosource | 0.05mg(Yeast) | 705 EUR |
Recombinant 30S ribosomal protein S7 (rpsG) |
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| MBS1217414-02mgEColi | MyBiosource | 0.2mg(E-Coli) | 635 EUR |
Recombinant 30S ribosomal protein S7 (rpsG) |
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| MBS1217414-05mgEColi | MyBiosource | 0.5mg(E-Coli) | 695 EUR |
Recombinant 60S ribosomal protein L4 (rpl-4) |
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| MBS1245409-005mgBaculovirus | MyBiosource | 0.05mg(Baculovirus) | 1135 EUR |
Recombinant 60S ribosomal protein L4 (rpl-4) |
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| MBS1245409-005mgEColi | MyBiosource | 0.05mg(E-Coli) | 880 EUR |
Recombinant 60S ribosomal protein L4 (rpl-4) |
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| MBS1245409-005mgYeast | MyBiosource | 0.05mg(Yeast) | 1010 EUR |
Homologous recombination technology generated recombinant pseudorabies virus expressing EGFP facilitates to evaluate its susceptibility to different cells and screen antiviral compounds
Pseudorabies virus (PRV) is considered as an emerging zoonotic pathogen since its isolation from a human case. Meanwhile, the disease caused by PRV infection has led huge economic losses to Chinese pig industry since 2011. In this study, we constructed a recombinant PRV stably expressing the enhanced green fluorescent protein (EGFP) by homologous recombination technology for evaluating its susceptibility to different human cell lines and screening antiviral compounds.
Stably expressed EGFP by this designed rPRVHuN-EGFP virus was confirmed in the infected cells, moreover, the growth kinetics of which was similar to that of wild type strain. Importantly, the application of this rPRV allowed us to easily verify its infectivity in all tested human cell lines, although the infection efficiencies were lower than that in PK15 cells. Meanwhile, the antiviral activities of harmine and PHA767491 were also conveniently validated in vitro, as directly reflected by the reduced EGFP signals. These results demonstrate that this recombinant PRV virus should be a useful tool for basic virology researches and antiviral agent screening.