Glycoengineering of pertuzumab and its impact on the pharmacokinetic/pharmacodynamic properties.

Abstract:

:Pertuzumab is an antihuman HER2 antibody developed for HER2 positive breast cancer. Glycosylation profiles are always the important issue for antibody based therapy. Previous findings have suggested the impact of glycosylation profiles on the function of antibodies, like pharmacodynamics, antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). However, the roles of fucose and sialic acid in the function of therapeutic antibodies still need further investigation, especially the role of sialic acid in nonfucosylated antibodies. This study focused on the pharmacokinetic and pharmacodynamic properties of pertuzumab after glycoengineering. Herein, nonfucosylated pertuzumab was produced in CHOFUT8-/- cells, and desialylated pertuzumab was generated by enzymatic hydrolysis. Present data indicated that fucose was critical for ADCC activity by influencing the interaction between pertuzumab and FcγRIIIa, nevertheless removal of sialic acid increased the ADCC and CDC activity of pertuzumab. Meanwhile, regarding to sialic acid, sialidase hydrolysis directly resulted in asialoglycoprotein receptors (ASGPRs) dependent clearance in hepatic cells in vitro. The pharmacokinetic assay revealed that co-injection of asialofetuin can protect desialylated pertuzumab against ASGPRs-mediated clearance. Taken together, the present study elucidated the importance of fucose and sialic acid for pertuzumab, and also provided further understanding of the relationship of glycosylation/pharmacokinetics/pharmacodynamics of therapeutic antibody.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Luo C,Chen S,Xu N,Wang C,Sai WB,Zhao W,Li YC,Hu XJ,Tian H,Gao XD,Yao WB

doi

10.1038/srep46347

subject

Has Abstract

pub_date

2017-04-11 00:00:00

pages

46347

issn

2045-2322

pii

srep46347

journal_volume

7

pub_type

杂志文章
  • Evaluation of circulating levels of CCN2/connective tissue growth factor in patients with ST-elevation myocardial infarction.

    abstract::CCN2/Connective tissue growth factor seems to be involved in development of cardiac hypertrophy and fibrosis, but a possible cardioprotective role in left ventricular (LV) remodelling following myocardial infarction has also been suggested. The main objectives of the study were therefore to investigate whether circula...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-12372-w

    authors: Ritschel V,Shetelig C,Seljeflot I,Limalanathan S,Hoffmann P,Halvorsen S,Arnesen H,Eritsland J,Andersen GØ

    更新日期:2017-09-20 00:00:00

  • Neural Network for Nanoscience Scanning Electron Microscope Image Recognition.

    abstract::In this paper we applied transfer learning techniques for image recognition, automatic categorization, and labeling of nanoscience images obtained by scanning electron microscope (SEM). Roughly 20,000 SEM images were manually classified into 10 categories to form a labeled training set, which can be used as a referenc...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-13565-z

    authors: Modarres MH,Aversa R,Cozzini S,Ciancio R,Leto A,Brandino GP

    更新日期:2017-10-16 00:00:00

  • Enhancement of recombination process using silver and graphene quantum dot embedded intermediate layer for efficient organic tandem cells.

    abstract::High performance of organic tandem solar cell is largely dependent on transparent and conductive intermediate layer (IML). The current work reports the design and fabrication of an IML using a simple solution process. The efficiency of a homo-tandem device with poly(3-hexylthiophene):phenyl-C61-butyric acid methyl est...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep30327

    authors: Ho NT,Tien HN,Jang SJ,Senthilkumar V,Park YC,Cho S,Kim YS

    更新日期:2016-07-25 00:00:00

  • Collective modes in multi-Weyl semimetals.

    abstract::We investigate collective modes in three dimensional (3D) gapless multi-Weyl semimetals with anisotropic energy band dispersions (i.e., with a positive integer J). For comparison, we also consider the gapless semimetals with the isotropic band dispersions (i.e. E ~ kJ). We calculate analytically long-wavelength plasma...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep34023

    authors: Ahn S,Hwang EH,Min H

    更新日期:2016-09-30 00:00:00

  • A Comparative Assessment of Human and Chimpanzee iPSC-derived Cardiomyocytes with Primary Heart Tissues.

    abstract::Comparative genomic studies in primates have the potential to reveal the genetic and mechanistic basis for human specific traits. These studies may also help us better understand inter-species phenotypic differences that are clinically relevant. Unfortunately, the obvious limitation on sample collection and experiment...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-33478-9

    authors: Pavlovic BJ,Blake LE,Roux J,Chavarria C,Gilad Y

    更新日期:2018-10-17 00:00:00

  • Increased Risk of Peptic Ulcers Following a Cholecystectomy for Gallstones.

    abstract::This retrospective cohort study examined the relationship between a cholecystectomy and the subsequent risk of peptic ulcers using a population-based database. Data for this study were retrieved from the Taiwan Longitudinal Health Insurance Database 2005. This study included 5209 patients who had undergone a cholecyst...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep30702

    authors: Tsai MC,Huang CC,Kao LT,Lin HC,Lee CZ

    更新日期:2016-07-29 00:00:00

  • Gene expression and proteomic analysis of shoot apical meristem transition from dormancy to activation in Cunninghamia lanceolata (Lamb.) Hook.

    abstract::In contrast to annual plants, in perennial plants, the shoot apical meristem (SAM) can undergo seasonal transitions between dormancy and activity; understanding this transition is crucial for understanding growth in perennial plants. However, little is known about the molecular mechanisms of SAM development in trees. ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep19938

    authors: Xu H,Cao D,Chen Y,Wei D,Wang Y,Stevenson RA,Zhu Y,Lin J

    更新日期:2016-02-02 00:00:00

  • Leakage of astrocyte-derived extracellular vesicles in stress-induced exhaustion disorder: a cross-sectional study.

    abstract::Patients with stress-induced exhaustion disorder (SED) demonstrate cognitive dysfunction similar to patients with minor traumatic brain injury (TBI). We have previously detected elevated concentrations of astrocyte-derived extracellular vesicles (EVs) in patients with TBI. As such, we hypothesized that astrocyte-deriv...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-021-81453-8

    authors: Wallensten J,Nager A,Åsberg M,Borg K,Beser A,Wilczek A,Mobarrez F

    更新日期:2021-01-21 00:00:00

  • Large seasonal and spatial variation in nano- and microphytoplankton diversity along a Baltic Sea-North Sea salinity gradient.

    abstract::Aquatic phytoplankton experience large fluctuations in environmental conditions during seasonal succession and across salinity gradients, but the impact of this variation on their diversity is poorly understood. We examined spatio-temporal variation in nano- and microphytoplankton (> 2 µm) community structure using al...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-74428-8

    authors: Olofsson M,Hagan JG,Karlson B,Gamfeldt L

    更新日期:2020-10-19 00:00:00

  • The impact of Fe atom on the spin-filter and spin thermoelectric properties of Au-Fe@C20-Au monomer and dimer systems.

    abstract::Based on density functional theory and non-equilibrium Green's function formalism, we explore the effect of Fe atom in Au-Fe@C20-Au monomer and dimer systems in comparison with the C20 fullerene molecular junctions. We calculate the spin-dependent transmission coefficient, spin polarization and also their spin thermoe...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-78111-w

    authors: Khalatbari H,Vishkayi SI,Soleimani HR

    更新日期:2020-12-03 00:00:00

  • Ontogeny of foraging behaviour in juvenile red-footed boobies (Sula sula).

    abstract::The early life stages represent a crucial period that can strongly influence population dynamics. We studied the development of foraging behaviour in the red-footed booby, a tropical seabird with an extensive post-fledging care period (3 to 6 months). Adults and juveniles were observed from shore and tracked at sea us...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-14478-7

    authors: Mendez L,Prudor A,Weimerskirch H

    更新日期:2017-10-24 00:00:00

  • Tandem Mass Tag (TMT)-based quantitative proteomics reveals potential targets associated with onset of Sub-clinical Mastitis in cows.

    abstract::Bovine milk is vital for infant nutrition and is a major component of the human diet. Bovine mastitis is a common inflammatory disease of mammary gland in cattle. It alters the immune profile of the animal and lowers the quality and yield of milk causing huge economic losses to dairy industry. The incidence of sub-cli...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-66211-6

    authors: Bathla S,Sindhu A,Kumar S,Dubey SK,Pattnaik S,Rawat P,Chopra A,Dang A,Kaushik JK,Mohanty AK

    更新日期:2020-06-09 00:00:00

  • Intradermal delivery of STAT3 siRNA to treat melanoma via dissolving microneedles.

    abstract::Hyperactivity of signal transducer and activity of transcription 3 (STAT3) plays a crucial role in melanoma invasion and metastasis. Gene therapy applying siRNA targeting STAT3 is a potential therapeutic strategy for melanoma. In this article, we first fabricated safe and novel dissolving microneedles (MNs) for topica...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-19463-2

    authors: Pan J,Ruan W,Qin M,Long Y,Wan T,Yu K,Zhai Y,Wu C,Xu Y

    更新日期:2018-01-18 00:00:00

  • Structural Analysis of an Evolved Transketolase Reveals Divergent Binding Modes.

    abstract::The S385Y/D469T/R520Q variant of E. coli transketolase was evolved previously with three successive smart libraries, each guided by different structural, bioinformatical or computational methods. Substrate-walking progressively shifted the target acceptor substrate from phosphorylated aldehydes, towards a non-phosphor...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep35716

    authors: Affaticati PE,Dai SB,Payongsri P,Hailes HC,Tittmann K,Dalby PA

    更新日期:2016-10-21 00:00:00

  • BCRP and P-gp relay overexpression in triple negative basal-like breast cancer cell line: a prospective role in resistance to Olaparib.

    abstract::The triple negative basal-like (TNBL) breast carcinoma is an aggressive and unfavorable prognosis disease. Inhibitors of poly(ADP-ribose) polymerase such as Olaparib could represent a promising targeted therapy but their sensitivity against Multidrug Resistance proteins (MDR), which causes resistance, is not well defi...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep12670

    authors: Dufour R,Daumar P,Mounetou E,Aubel C,Kwiatkowski F,Abrial C,Vatoux C,Penault-Llorca F,Bamdad M

    更新日期:2015-08-03 00:00:00

  • Down-regulation of microRNA-144 in air pollution-related lung cancer.

    abstract::Air pollution has been classified as a group 1 carcinogen in humans, but the underlying tumourigenic mechanisms remain unclear. In Xuanwei city of Yunnan Province, the lung cancer incidence is among the highest in China, owing to severe air pollution generated by the combustion of smoky coal, providing a unique opport...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep14331

    authors: Pan HL,Wen ZS,Huang YC,Cheng X,Wang GZ,Zhou YC,Wang ZY,Guo YQ,Cao Y,Zhou GB

    更新日期:2015-09-23 00:00:00

  • Exploration of the relationship between biogas production and microbial community under high salinity conditions.

    abstract::High salinity frequently causes inhibition and even failure in anaerobic digestion. To explore the impact of increasing NaCl concentrations on biogas production, and reveal the microbial community variations in response to high salinity stress, the Illumina high-throughput sequencing technology was employed. The resul...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-01298-y

    authors: Wang S,Hou X,Su H

    更新日期:2017-04-25 00:00:00

  • Superconductivity at 52 K in hydrogen-substituted LaFeAsO(1-x)Hx under high pressure.

    abstract::The 1111-type iron-based superconductor LnFeAsO(1-x)Fx (Ln stands for lanthanide) is the first material with a Tc above 50 K, other than cuprate superconductors. Electron doping into LaFeAsO by H, rather than F, revealed a double-dome-shaped Tc-x diagram, with a first dome (SC1, 0.05

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep07829

    authors: Takahashi H,Soeda H,Nukii M,Kawashima C,Nakanishi T,Iimura S,Muraba Y,Matsuishi S,Hosono H

    更新日期:2015-01-16 00:00:00

  • Modelling survival: exposure pattern, species sensitivity and uncertainty.

    abstract::The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep29178

    authors: Ashauer R,Albert C,Augustine S,Cedergreen N,Charles S,Ducrot V,Focks A,Gabsi F,Gergs A,Goussen B,Jager T,Kramer NI,Nyman AM,Poulsen V,Reichenberger S,Schäfer RB,Van den Brink PJ,Veltman K,Vogel S,Zimmer EI,Preuss

    更新日期:2016-07-06 00:00:00

  • Modulation of yellow expression contributes to thermal plasticity of female abdominal pigmentation in Drosophila melanogaster.

    abstract::Phenotypic plasticity describes the ability of a given genotype to produce distinct phenotypes in different environments. We use the temperature sensitivity of abdominal pigmentation in Drosophila melanogaster females as a model to analyse the effect of the environment on development. We reported previously that therm...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep43370

    authors: Gibert JM,Mouchel-Vielh E,Peronnet F

    更新日期:2017-02-23 00:00:00

  • Microsatellite Borders and Micro-sequence Conservation in Juglans.

    abstract::Walnuts (Juglans spp.) are economically important nut and timber species with a worldwide distribution. Using the published Persian walnut genome as a reference for the assembly of short reads from six Juglans species and several interspecific hybrids, we identified simple sequence repeats in 12 Juglans nuclear and or...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-39793-z

    authors: Ebrahimi A,Mathur S,Lawson SS,LaBonte NR,Lorch A,Coggeshall MV,Woeste KE

    更新日期:2019-03-06 00:00:00

  • Mass flux decay timescales of volcanic particles due to aeolian processes in the Argentinian Patagonia steppe.

    abstract::We investigate the timescales of the horizontal mass flux decay of wind remobilised volcanic particles in Argentina, associated with the tephra-fallout deposit produced by the 2011-2012 Cordón Caulle (Chile) eruption. Particle removal processes are controlled by complex interactions of meteorological conditions, surfa...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-71022-w

    authors: Dominguez L,Rossi E,Mingari L,Bonadonna C,Forte P,Panebianco JE,Bran D

    更新日期:2020-09-02 00:00:00

  • Harmonic radar tracking reveals random dispersal pattern of bumblebee (Bombus terrestris) queens after hibernation.

    abstract::The dispersal of animals from their birth place has profound effects on the immediate survival and longer-term persistence of populations. Molecular studies have estimated that bumblebee colonies can be established many kilometers from their queens' natal nest site. However, little is known about when and how queens d...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-019-40355-6

    authors: Makinson JC,Woodgate JL,Reynolds A,Capaldi EA,Perry CJ,Chittka L

    更新日期:2019-03-20 00:00:00

  • First record of Podocarpoid fossil wood in South China.

    abstract::A new species of fossil conifer wood, Podocarpoxylon donghuaiense sp. nov., is described from the late Eocene of Nadu Formation in Baise Basin of the Guangxi Province, South China. This fossil wood is characterized by distinct growth rings, circular to oval tracheids in cross section, 1-2-seriate opposite pits on radi...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep32294

    authors: Li L,Jin JH,Quan C,Oskolski AA

    更新日期:2016-08-30 00:00:00

  • Silicon-core glass fibres as microwire radial-junction solar cells.

    abstract::Vertically aligned radial-junction solar cell designs offer potential improvements over planar geometries, as carrier generation occurs close to the junction for all absorption depths, but most production methods still require a single crystal substrate. Here, we report on the fabrication of such solar cells from poly...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep06283

    authors: Martinsen FA,Smeltzer BK,Nord M,Hawkins T,Ballato J,Gibson UJ

    更新日期:2014-09-04 00:00:00

  • Oxidative Stress is a Convincing Contributor to Idiopathic Chronic Fatigue.

    abstract::The linkage between oxidative stress and idiopathic chronic fatigue (ICF) has not been explored in detail. This study thoroughly compared the serum levels of biomarkers for oxidative stress and antioxidants from 103 subjects with ICF (20 men and 83 women) to those of 82 healthy volunteers (27 men and 55 women). Oxidat...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-31270-3

    authors: Lee JS,Kim HG,Lee DS,Son CG

    更新日期:2018-08-27 00:00:00

  • Thiamine tetrahydrofurfuryl disulfide promotes voluntary activity through dopaminergic activation in the medial prefrontal cortex.

    abstract::A physically active lifestyle is associated with better health in body and mind, and it is urgent that supporting agents for such lifestyles be developed. In rodents, voluntary locomotor activity as an active physical behavior may be mediated by dopaminergic neurons (DNs). Thiamine phosphate esters can stimulate DNs, ...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-018-28462-2

    authors: Saiki M,Matsui T,Soya M,Kashibe T,Shima T,Shimizu T,Naruto T,Kitayoshi T,Akimoto K,Ninomiya S,Soya H

    更新日期:2018-07-11 00:00:00

  • Coordinated vigilance provides evidence for direct reciprocity in coral reef fishes.

    abstract::Reciprocity is frequently assumed to require complex cognitive abilities. Therefore, it has been argued that reciprocity may be restricted to animals that can meet these demands. Here, we provide evidence for the potential presence of direct reciprocity in teleost fishes. We demonstrate that in pairs of coral reef rab...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/srep14556

    authors: Brandl SJ,Bellwood DR

    更新日期:2015-09-25 00:00:00

  • Differential activation of endocrine-immune networks by arthritis challenge: Insights from colony-specific responses.

    abstract::Rheumatoid arthritis (RA) is a chronic inflammatory condition with variable clinical presentation and disease progression. Importantly, animal models of RA are widely used to examine disease pathophysiology/treatments. Here, we exploited known vendor colony-based differences in endocrine/immune responses to gain insig...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-017-00652-4

    authors: Bodnar TS,Taves MD,Lavigne KM,Woodward TS,Soma KK,Weinberg J

    更新日期:2017-04-06 00:00:00

  • Characterisation of cuticular inflation development and ultrastructure in Trichuris muris using correlative X-ray computed tomography and electron microscopy.

    abstract::The parasitic nematode Trichuris trichiura is a significant burden on public health in developing countries, and currently available drugs exhibit a poor cure rate. Worms live within a specialised tunnel of host intestinal epithelial cells and have anterior-ventral projections of the cuticle termed "cuticular inflatio...

    journal_title:Scientific reports

    pub_type: 杂志文章

    doi:10.1038/s41598-020-61916-0

    authors: O'Sullivan JDB,Cruickshank SM,Starborg T,Withers PJ,Else KJ

    更新日期:2020-04-03 00:00:00