Abstract：
:The success of antibody therapeutics is strongly influenced by their multifunctional nature that couples antigen recognition mediated by their variable regions with effector functions and half-life extension mediated by a subset of their constant regions. Nevertheless, the monospecific IgG format is not optimal for many therapeutic applications, and this has led to the design of a vast number of unique multispecific antibody formats that enable targeting of multiple antigens or multiple epitopes on the same antigen. Despite the diversity of these formats, a common challenge in generating multispecific antibodies is that they display suboptimal physical and chemical properties relative to conventional IgGs and are more difficult to develop into therapeutics. Here we review advances in the design and engineering of multispecific antibodies with drug-like properties, including favorable stability, solubility, viscosity, specificity and pharmacokinetic properties. We also highlight emerging experimental and computational methods for improving the next generation of multispecific antibodies, as well as their constituent antibody fragments, with natural IgG-like properties. Finally, we identify several outstanding challenges that need to be addressed to increase the success of multispecific antibodies in the clinic.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Sawant MS,Streu CN,Wu L,Tessier PMdoi
10.3390/ijms21207496subject
Has Abstractpub_date
2020-10-12 00:00:00issue
20issn
1422-0067pii
ijms21207496journal_volume
21pub_type
杂志文章,评审abstract：:A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiati...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms161125942
更新日期：2015-11-02 00:00:00
abstract：:Modern antipsychotic drugs are employed increasingly in the treatment of mood disorders as well as psychoses, stimulating interest in their possible contributions to altering suicidal risk. Clozapine remains the only treatment with an FDA-recognized indication for reducing suicidal risk (in schizophrenia). We carried ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms17101700
更新日期：2016-10-11 00:00:00
abstract：:Inhibition of cholinesterases remains one of a few available treatment strategies for neurodegenerative dementias such as Alzheimer's disease and related conditions. The current study was inspired by previous data on anticholinesterase properties of diterpenoids from Perovskia atriplicifolia and other Lamiaceae specie...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21124475
更新日期：2020-06-23 00:00:00
abstract：:Presently, many studies have focused on exploring in silico approaches in the identification and development of alternative therapy for the treatment and management of cancer. Solute carrier family-2-member-4-gene (Slc2a4) which encodes glucose transporter 4 protein (GLUT4), has been identified as a promising therapeu...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19020386
更新日期：2018-01-28 00:00:00
abstract：:It has been confirmed that alternatively activated macrophages (M2) participate in tissue remodeling and fibrosis occurrence, but the effect of M2 on peritoneal fibrosis related to peritoneal dialysis (PD) hasn't been elucidated. This study was therefore conducted to assess the association between M2 and peritoneal fi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms140510369
更新日期：2013-05-17 00:00:00
abstract：:Seed storability, defined as the ability to remain alive during storage, is an important agronomic and physiological characteristic, but the underlying genetic mechanism remains largely unclear. Here, we report quantitative trait loci (QTLs) analyses for seed storability using a high-density single nucleotide polymorp...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20184442
更新日期：2019-09-09 00:00:00
abstract：:(1) Background: A high incidence of intervening sequence (IVS)4+919 G>A mutation with later-onset cardiac phenotype have been reported in a majority of Taiwan Fabry cohorts. Some evidence indicated that conventional biomarkers failed to predict the long-term progression and therapeutic outcome; (2) Methods: In this st...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19051480
更新日期：2018-05-16 00:00:00
abstract：:One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms14059379
更新日期：2013-04-29 00:00:00
abstract：:Brugada syndrome (BrS) is an inherited electrical heart disease associated with a high risk of sudden cardiac death (SCD). The genetic characterization of BrS has always been challenging. Although several cardiac ion channel genes have been associated with BrS, SCN5A is the only gene that presents definitive evidence ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21228556
更新日期：2020-11-13 00:00:00
abstract：:Mycobacterium immunogenum, a newly identified member of the Mycobacterium chelonae_M. abscessus complex is considered a potential etiological agent for hypersensitivity pneumonitis (HP) in machine workers exposed to contaminated metalworking fluid (MWF). This study investigated the biocidal efficacy of the frequently ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms12010725
更新日期：2011-01-20 00:00:00
abstract：:Apolipoprotein E (APOE) ε4 gene allele and type 2 diabetes mellitus (T2DM) are prime risk factors for Alzheimer's disease (AD). Despite evidence linking T2DM and apoE4, the mechanism underlying their interaction is yet to be determined. In the present study, we employed a model of APOE-targeted replacement mice and hi...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21041289
更新日期：2020-02-14 00:00:00
abstract：:To elucidate the molecular details of the activation-associated clustering of epidermal growth factor receptors (EGFRs), the time course of the mobility and aggregation states of eGFP tagged EGFR in the membranes of Chinese hamster ovary (CHO) cells was assessed by in situ mobility assays. Fluorescence correlation spe...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20133370
更新日期：2019-07-09 00:00:00
abstract：:Curcumin diglutaric acid (CurDG), an ester prodrug of curcumin, has the potential to be developed as an anti-inflammatory agent due to its improved solubility and stability. In this study, the anti-inflammatory effects of CurDG were evaluated. The effects of CurDG on inflammatory mediators were evaluated in LPS-stimul...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21165700
更新日期：2020-08-09 00:00:00
abstract：:Metallothioneins (MTs) are a family of metal-binding proteins virtually expressed in all organisms including prokaryotes, lower eukaryotes, invertebrates and mammals. These proteins regulate homeostasis of zinc (Zn) and copper (Cu), mitigate heavy metal poisoning, and alleviate superoxide stress. In recent years, MTs ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18102197
更新日期：2017-10-23 00:00:00
abstract：:The rapidly activating delayed rectifier potassium current (IKr) plays a critical role in cardiac repolarization. Although IKr is known to be regulated by both α1- and β1-adrenergic receptors (ARs), the cross-talk and feedback mechanisms that dictate its response to α1- and β1-AR activation are not known. In the prese...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms150814220
更新日期：2014-08-15 00:00:00
abstract：:Blood rheology is a key determinant of tissue perfusion at rest and during exercise. The present study investigated the effects of race distance on hematological, blood rheological, and red blood cell (RBC) senescence parameters. Eleven runners participated in the Martigny-Combes à Chamonix 40 km race (MCC, elevation ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21228531
更新日期：2020-11-12 00:00:00
abstract：:Myeloid immune cells, such as dendritic cells, monocytes, and macrophages, play a central role in the generation of immune responses and thus are often either disabled or even hijacked by tumors. These new tolerogenic activities of tumor-associated myeloid cells are controlled by an oncogenic transcription factor, sig...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19061803
更新日期：2018-06-19 00:00:00
abstract：:The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans. At the present, there is no single specific ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21072272
更新日期：2020-03-25 00:00:00
abstract：:Combating malaria is almost a never-ending battle, as Plasmodium parasites develop resistance to the drugs used against them, as observed recently in artemisinin-based combination therapies. The main concern now is if the resistant parasite strains spread from Southeast Asia to Africa, the continent hosting most malar...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms20225574
更新日期：2019-11-08 00:00:00
abstract：:Recent data show that cardiac hypertrophy contributes substantially to the overall heart failure burden. Mitochondrial dysfunction is a common feature of cardiac hypertrophy. Recent studies have reported that isosteviol inhibits myocardial ischemia-reperfusion injury in guinea pigs and H9c2 cells. This work investigat...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms21020682
更新日期：2020-01-20 00:00:00
abstract：: Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor which is activated by increases in adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio and/or adenosine diphosphate (ADP)/ATP ratio, and increases different metabolic pathways such as fatty acid oxidation, glucose trans...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18020288
更新日期：2017-01-29 00:00:00
abstract：:DExD (DDX)- and DExH (DHX)-box RNA helicases, named after their Asp-Glu-x-Asp/His motifs, are integral to almost all RNA metabolic processes in eukaryotic cells. They play myriad roles in processes ranging from transcription and mRNA-protein complex remodeling, to RNA decay and translation. This last facet, translatio...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21124402
更新日期：2020-06-20 00:00:00
abstract：:Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms19030808
更新日期：2018-03-11 00:00:00
abstract：:Some engineered nanomaterials (ENMs) may have the potential to cause damage to the genetic material in living systems. The mechanistic machinery functioning at the cellular/molecular level, in the form of DNA repair processes, has evolved to help circumvent DNA damage caused by exposure to a variety of foreign substan...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms18071515
更新日期：2017-07-13 00:00:00
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journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms160715688
更新日期：2015-07-10 00:00:00
abstract：:Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Due to micrometastatic spread, radical surgery alone rarely results in cure. Introduction of combination chemotherapy in the 1970s, however, dramatically increased overall survival rates from 20% to approximately 70%. Unfortunat...
journal_title：International journal of molecular sciences
pub_type： 杂志文章,评审
doi：10.3390/ijms21186885
更新日期：2020-09-19 00:00:00
abstract：:Altered microRNA expression is implicated in cardiovascular diseases. Our objective was to determine microRNA signatures in thoracic aortic aneurysms (TAAs) and abdominal aortic aneurysms (AAAs) compared with control non-aneurysmal aortic specimens. We evaluated the expression of fifteen selected microRNA in human TAA...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms18040875
更新日期：2017-04-20 00:00:00
abstract：:The rs10830963 variant of the Melatonin Receptor 1B (MTNR1B) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/G risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. Design: In...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19123734
更新日期：2018-11-23 00:00:00
abstract：:Consecutive treatment of adult rat heart with isoproterenol and adenosine (Iso/Aden), known to consecutively activate PKA/PKC signaling, is cardioprotective against ischemia and reperfusion (I/R). Whether this is cardioprotective in an immature heart is unknown. Langendorff-perfused hearts from adult and immature (60 ...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms19020494
更新日期：2018-02-07 00:00:00
abstract：:In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (...
journal_title：International journal of molecular sciences
pub_type： 杂志文章
doi：10.3390/ijms151223909
更新日期：2014-12-22 00:00:00
