Open AccessReview
Current Controversies in Lupus Anticoagulant Detection
Antibodies 2016, 5(4), 22; doi:10.3390/antib5040022 -
Abstract
Antiphospholipid syndrome is an autoimmune, acquired thrombophilia diagnosed when vascular thrombosis or pregnancy morbidity are accompanied by persistent antiphospholipid antibodies. Lupus anticoagulants (LA) are one of the criteria antibodies but calibration plasmas are unavailable and they are detected by inference based on antibody
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Antiphospholipid syndrome is an autoimmune, acquired thrombophilia diagnosed when vascular thrombosis or pregnancy morbidity are accompanied by persistent antiphospholipid antibodies. Lupus anticoagulants (LA) are one of the criteria antibodies but calibration plasmas are unavailable and they are detected by inference based on antibody behaviour in a medley of coagulation-based assays. Elevated screening tests suggest the presence of a LA, which is confirmed with mixing tests to evidence inhibition and confirmatory tests to demonstrate phospholipid-dependence. At least two screening tests of different principle must be used to account for antibody heterogeneity and controversy exists on whether assays, in addition to dilute Russell’s viper venom time and activated partial thromboplastin time, should be employed. A variety of approaches to raw data manipulation and interpretation attract debate, as does inclusion or exclusion of mixing studies in circumstances where the presence of a LA is already evident from other results. Therapeutic anticoagulation compromises coagulation-based assays but careful data interpretation and use of alternative reagents can detect or exclude LA in specific circumstances, and this aspect of LA detection continues to evolve. This review focuses on the main areas of debate in LA detection. Full article
Open AccessReview
Surveillance for Intracellular Antibody by Cytosolic Fc Receptor TRIM21
Antibodies 2016, 5(4), 21; doi:10.3390/antib5040021 -
Abstract
TRIM21 has emerged as an atypical Fc receptor that is broadly conserved and widely expressed in the cytoplasm of mammalian cells. Viruses that traffic surface-bound antibodies into the cell during infection recruit TRIM21 via a high affinity interaction between Fc and TRIM21 PRYSPRY
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TRIM21 has emerged as an atypical Fc receptor that is broadly conserved and widely expressed in the cytoplasm of mammalian cells. Viruses that traffic surface-bound antibodies into the cell during infection recruit TRIM21 via a high affinity interaction between Fc and TRIM21 PRYSPRY domain. Following binding of intracellular antibody, TRIM21 acts as both antiviral effector and sensor for innate immune signalling. These activities serve to reduce viral replication by orders of magnitude in vitro and contribute to host survival during in vivo infection. Neutralization occurs rapidly after detection and requires the activity of the ubiquitin-proteasome system. The microbial targets of this arm of intracellular immunity are still being identified: TRIM21 activity has been reported following infection by several non-enveloped viruses and intracellular bacteria. These findings extend the sphere of influence of antibodies to the intracellular domain and have broad implications for immunity. TRIM21 has been implicated in the chronic auto-immune condition systemic lupus erythematosus and is itself an auto-antigen in Sjögren’s syndrome. This review summarises our current understanding of TRIM21’s role as a cytosolic Fc receptor and briefly discusses pathological circumstances where intracellular antibodies have been described, or are hypothesized to occur, and may benefit from further investigations of the role of TRIM21. Full article
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Open AccessArticle
Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally
Antibodies 2016, 5(4), 20; doi:10.3390/antib5040020 -
Abstract
Nanoparticles (NPs) are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n.) priming followed by i.n. or subcutaneous (s.c.) boosting immunization affects the humoral immune
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Nanoparticles (NPs) are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n.) priming followed by i.n. or subcutaneous (s.c.) boosting immunization affects the humoral immune response to chicken ovalbumin (Ova) and Ova conjugated to 20 nm NPs (NP-Ova). We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA). In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses. Full article
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Open AccessReview
Antibody Aggregation: Insights from Sequence and Structure
Antibodies 2016, 5(3), 19; doi:10.3390/antib5030019 -
Abstract
Monoclonal antibodies (mAbs) are the fastest-growing biological therapeutics with important applications ranging from cancers, autoimmunity diseases and metabolic disorders to emerging infectious diseases. Aggregation of mAbs continues to be a major problem in their developability. Antibody aggregation could be triggered by partial unfolding
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Monoclonal antibodies (mAbs) are the fastest-growing biological therapeutics with important applications ranging from cancers, autoimmunity diseases and metabolic disorders to emerging infectious diseases. Aggregation of mAbs continues to be a major problem in their developability. Antibody aggregation could be triggered by partial unfolding of its domains, leading to monomer-monomer association followed by nucleation and growth. Although the aggregation propensities of antibodies and antibody-based proteins can be affected by the external experimental conditions, they are strongly dependent on the intrinsic antibody properties as determined by their sequences and structures. In this review, we describe how the unfolding and aggregation susceptibilities of IgG could be related to their cognate sequences and structures. The impact of antibody domain structures on thermostability and aggregation propensities, and effective strategies to reduce aggregation are discussed. Finally, the aggregation of antibody-drug conjugates (ADCs) as related to their sequence/structure, linker payload, conjugation chemistry and drug-antibody ratio (DAR) is reviewed. Full article
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Open AccessReview
Antiphospholipid Antibodies: From General Concepts to Its Relation with Malignancies
Antibodies 2016, 5(3), 18; doi:10.3390/antib5030018 -
Abstract
Antiphospholipid syndrome (APS) is an adquired autoimmune pro-thrombotic disease characterized by arterial and/or venous thrombosis and/or fetal losses associated with the persistent presence of antiphospholipid antibodies (aPL) detectable by solid phase assays (anticardiolipin (aCL) and anti-β2 glycoprotein I, β2GPI) and/or functional coagulation test
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Antiphospholipid syndrome (APS) is an adquired autoimmune pro-thrombotic disease characterized by arterial and/or venous thrombosis and/or fetal losses associated with the persistent presence of antiphospholipid antibodies (aPL) detectable by solid phase assays (anticardiolipin (aCL) and anti-β2 glycoprotein I, β2GPI) and/or functional coagulation test (lupus anticoagulant (LA)). Most patients with typical APS manifestations have the presence of one or more of conventional aPL, but, some patients might exhibit clinical features related with APS but with persistent negative determinations of “classic” aPL (seronegative APS). Expanding the network of autoantibodies in patients highly suspected of having APS but who have normal results from a conventional test using new antibodies (i.e., phosphatidylserine/prothrombin and β2GPI domain 1) would increase the diagnosis. Thrombosis is one of the leading causes of death among patients with cancer, representing up to 15% of all deaths. Cancer increases the risk of thrombosis and chemotherapy is further associated with a higher risk of thrombosis. In addition, aPL may contribute to an increased risk of thrombosis in patients with malignancies, although the levels do not seem to reflect their pathogenicity. Several malignancies, particularly hematological and lymphoproliferative malignancies, may indeed be associated with the generation of aPL but do not necessarily enhance the thrombophilic risk in these patients. Full article
Open AccessReview
Antiphospholipid Syndrome and Kidney Involvement: New Insights
Antibodies 2016, 5(3), 17; doi:10.3390/antib5030017 -
Abstract
Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thromboses and pregnancy morbidity associated with antiphospholipid antibodies: lupus anticoagulant, IgG or IgM anticardiolipin or anti-beta 2-glycoprotein I. The kidney is one of the major target organs in antiphospholipid syndrome (APS). However, beyond the
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Antiphospholipid syndrome is an autoimmune disorder characterized by vascular thromboses and pregnancy morbidity associated with antiphospholipid antibodies: lupus anticoagulant, IgG or IgM anticardiolipin or anti-beta 2-glycoprotein I. The kidney is one of the major target organs in antiphospholipid syndrome (APS). However, beyond the known involvement of the kidney in primary and associated APS, we may be observing a new form of APS within the context of renal failure. This review describes the classical kidney manifestations of APS and provides new considerations to be taken into account. Full article
Open AccessReview
The Significance of Anti-Beta-2-Glycoprotein I Antibodies in Antiphospholipid Syndrome
Antibodies 2016, 5(2), 16; doi:10.3390/antib5020016 -
Abstract
Antiphospholipid syndrome (APS) is a thrombophilic disorder that classically presents with vascular thrombosis and/or obstetric complications. APS is associated with antiphospholipid antibodies: a heterogeneous group of autoantibodies that are directed against membrane phospholipids in complex with phospholipid-binding proteins. Beta-2-glycoprotein I (B2GPI) binds anionic
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Antiphospholipid syndrome (APS) is a thrombophilic disorder that classically presents with vascular thrombosis and/or obstetric complications. APS is associated with antiphospholipid antibodies: a heterogeneous group of autoantibodies that are directed against membrane phospholipids in complex with phospholipid-binding proteins. Beta-2-glycoprotein I (B2GPI) binds anionic phospholipids and is considered to be the predominant antigen in APS and antibodies against B2GPI (anti-B2GPI) are recognised in the laboratory criteria for APS diagnosis. This review focuses on the part played by anti-B2GPI in the pathogenesis of APS, their associations with different clinical phenotypes of the disorder and new avenues for refining the diagnostic potential of anti-B2GPI testing. Full article
Open AccessReview
Antiphospholipid Antibodies: Their Origin and Development
Antibodies 2016, 5(2), 15; doi:10.3390/antib5020015 -
Abstract
Antiphospholipid antibodies (aPL) are a hallmark of the antiphospholipid syndrome (APS), which is the most commonly acquired thrombophilia. To date there is consensus that aPL cause the clinical manifestations of this potentially devastating disorder. However, there is good evidence that not all aPL
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Antiphospholipid antibodies (aPL) are a hallmark of the antiphospholipid syndrome (APS), which is the most commonly acquired thrombophilia. To date there is consensus that aPL cause the clinical manifestations of this potentially devastating disorder. However, there is good evidence that not all aPL are pathogenic. For instance, aPL associated with syphilis show no association with the manifestations of APS. While there has been intensive research on the pathogenetic role of aPL, comparably little is known about the origin and development of aPL. This review will summarize the current knowledge and understanding of the origin and development of aPL derived from animal and human studies. Full article
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Open AccessArticle
A Clinical Approach for Defining the Threshold between Low and Medium Anti-Cardiolipin Antibody Levels for QUANTA Flash Assays
Antibodies 2016, 5(2), 14; doi:10.3390/antib5020014 -
Abstract
The threshold between low and medium antibody levels for anticardiolipin (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) for the diagnosis of antiphospholipid syndrome (APS) remains a matter of discussion. Our goal was to create a protocol for determining the low/medium antibody cut-off for
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The threshold between low and medium antibody levels for anticardiolipin (aCL) and anti-β2 glycoprotein I antibodies (aβ2GPI) for the diagnosis of antiphospholipid syndrome (APS) remains a matter of discussion. Our goal was to create a protocol for determining the low/medium antibody cut-off for aCL antibody methods based on a clinical approach, and utilize it to establish the clinically-relevant low/medium threshold for QUANTA Flash aCL chemiluminescent immunoassay (CIA) results. The study included 288 samples from patients with primary APS (n = 70), secondary APS (n = 42), suspected APS (n = 36), systemic lupus erythematosus (SLE) without APS (n = 96) and other connective tissue diseases (n = 44). All samples were tested for IgG and IgM aCL antibodies with QUANTA Flash CIA, along with traditional enzyme-linked immunosorbent assays (ELISAs) (QUANTA Lite). The assay specific low/medium threshold for QUANTA Flash aCL IgG and IgM assays (i.e., the equivalent of 40 GPL and MPL units) was established as 95 and 31 chemiluminescent units (CU), respectively, based on clinical performance and comparison to QUANTA Lite ELISAs. Agreement between CIA and ELISA assay results improved substantially when the platform-specific low/medium antibody threshold was used, as compared to agreement obtained on results generated with the assay cutoff: Cohen’s kappa increased from 0.85 to 0.91 for IgG aCL, and from 0.59 to 0.75 for IgM aCL results. This study describes a clinical approach for establishing the low/medium antibody threshold for aPL antibody assays, and successfully employs it to define 95 and 31 CU, respectively, as the low/medium cut point for QUANTA Flash aCL IgG and IgM results. This study can serve as a model for labs wishing to establish the appropriate low/medium aPL antibody threshold when implementing new aPL antibody assays. Full article
Open AccessArticle
Binding Analysis of Human Immunoglobulin G as a Zinc-Binding Protein
Antibodies 2016, 5(2), 13; doi:10.3390/antib5020013 -
Abstract
Human immunoglobulin G (IgG) binding with zinc ions was examined using zinc ions immobilized on chelating Sepharose beads (Zn-beads). Human IgG bound to Zn-beads but not to Sepharose beads (control beads). Mouse, rat, bovine and equine IgGs also bound to Zn-beads, similar to
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Human immunoglobulin G (IgG) binding with zinc ions was examined using zinc ions immobilized on chelating Sepharose beads (Zn-beads). Human IgG bound to Zn-beads but not to Sepharose beads (control beads). Mouse, rat, bovine and equine IgGs also bound to Zn-beads, similar to human IgG. The human IgG F(c) fragment showed zinc ion–binding activity whereas the Fab fragment did not. Ethylenediaminetetraacetic acid (EDTA)-treated Zn-beads no longer bound human IgG; however, washing the beads, followed by the addition of zinc ions, restored the binding activity towards human IgG. Zn-beads saturated with human fibrinogen could bind human IgG, and Zn-beads saturated with human IgG could bind fibrinogen. These results suggest that animal IgGs, including human, specifically bind zinc ions, probably through a zinc-binding site in the F(c) fragment and not in the Fab fragment. In addition, IgG and fibrinogen interact with each other and/or bind zinc ions through different mechanisms. Full article
Open AccessReview
β2GP1, Anti-β2GP1 Antibodies and Platelets: Key Players in the Antiphospholipid Syndrome
Antibodies 2016, 5(2), 12; doi:10.3390/antib5020012 -
Abstract
Anti-beta 2 glycoprotein 1 (anti-β2GP1) antibodies are commonly found in patients with autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Their presence is highly associated with increased risk of vascular thrombosis and/or recurrent pregnancy-related complications. Although
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Anti-beta 2 glycoprotein 1 (anti-β2GP1) antibodies are commonly found in patients with autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Their presence is highly associated with increased risk of vascular thrombosis and/or recurrent pregnancy-related complications. Although they are a subtype of anti-phospholipid (APL) antibody, anti-β2GP1 antibodies form complexes with β2GP1 before binding to different receptors associated with anionic phospholipids on structures such as platelets and endothelial cells. β2GP1 consists of five short consensus repeat termed “sushi” domains. It has three interchangeable conformations with a cryptic epitope at domain 1 within the molecule. Anti-β2GP1 antibodies against this cryptic epitope are referred to as ‘type A’ antibodies, and have been suggested to be more strongly associated with both vascular and obstetric complications. In contrast, ‘type B’ antibodies, directed against other domains of β2GP1, are more likely to be benign antibodies found in asymptomatic patients and healthy individuals. Although the interactions between anti-β2GP1 antibodies, β2GP1, and platelets have been investigated, the actual targeted metabolic pathway(s) and/or receptor(s) involved remain to be clearly elucidated. This review will discuss the current understanding of the interaction between anti-β2GP1 antibodies and β2GP1, with platelet receptors and associated signalling pathways. Full article
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Open AccessReview
Generating Recombinant Antibodies to Membrane Proteins through Phage Display
Antibodies 2016, 5(2), 11; doi:10.3390/antib5020011 -
Abstract
One of the most important classes of proteins in terms of drug targets is cell surface membrane proteins, and yet it is a challenging set of proteins for generating high-quality affinity reagents. In this review, we focus on the use of phage libraries,
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One of the most important classes of proteins in terms of drug targets is cell surface membrane proteins, and yet it is a challenging set of proteins for generating high-quality affinity reagents. In this review, we focus on the use of phage libraries, which display antibody fragments, for generating recombinant antibodies to membrane proteins. Such affinity reagents generally have high specificity and affinity for their targets. They have been used for cell staining, for promoting protein crystallization to solve three-dimensional structures, for diagnostics, and for treating diseases as therapeutics. We cover publications on this topic from the past 10 years, with a focus on the various formats of membrane proteins for affinity selection and the diverse affinity selection strategies used. Lastly, we discuss the challenges faced in this field and provide possible directions for future efforts. Full article
Open AccessCorrection
Correction: Cytokines in the Germinal Center Niche Antibodies 2016, 5(1), 5
Antibodies 2016, 5(2), 10; doi:10.3390/antib5020010 -
Abstract The following corrections should be made to the references and bibliography of the published paper [1]:[...] Full article
Open AccessReview
Autoantibodies in Neuropsychiatric Disorders
Antibodies 2016, 5(2), 9; doi:10.3390/antib5020009 -
Abstract
Little is known about the etiology of neuropsychiatric disorders. The identification of autoantibodies targeting the N-methyl-d-aspartate receptor (NMDA-R), which causes neurological and psychiatric symptoms, has reinvigorated the hypothesis that other patient subgroups may also suffer from an underlying autoimmune condition.
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Little is known about the etiology of neuropsychiatric disorders. The identification of autoantibodies targeting the N-methyl-d-aspartate receptor (NMDA-R), which causes neurological and psychiatric symptoms, has reinvigorated the hypothesis that other patient subgroups may also suffer from an underlying autoimmune condition. In recent years, a wide range of neuropsychiatric diseases and autoantibodies targeting ion-channels or neuronal receptors including NMDA-R, voltage gated potassium channel complex (VGKC complex), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R), γ-aminobutyric acid receptor (GABA-R) and dopamine receptor (DR) were studied and conflicting reports have been published regarding the seroprevalence of these autoantibodies. A clear causative role of autoantibodies on psychiatric symptoms has as yet only been shown for the NMDA-R. Several other autoantibodies have been related to the presence of certain symptoms and antibody effector mechanisms have been proposed. However, extensive clinical studies with large multicenter efforts to standardize diagnostic procedures for autoimmune etiology and animal studies are needed to confirm the pathogenicity of these autoantibodies. In this review, we discuss the current knowledge of neuronal autoantibodies in the major neuropsychiatric disorders: psychotic, major depression, autism spectrum, obsessive-compulsive and attention-deficit/hyperactivity disorders. Full article
Open AccessReview
Epigenetic Regulation of Innate Immunity by microRNAs
Antibodies 2016, 5(2), 8; doi:10.3390/antib5020008 -
Abstract
The innate immune response, which is usually referred to as the first line of defense, protects the hosts against pathogenic micro-organisms. Some of the biomolecules released from the pathogens, such as proteins, lipoproteins and nucleic acids, which are collectively termed as pathogen-associated molecular
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The innate immune response, which is usually referred to as the first line of defense, protects the hosts against pathogenic micro-organisms. Some of the biomolecules released from the pathogens, such as proteins, lipoproteins and nucleic acids, which are collectively termed as pathogen-associated molecular patterns (PAMPs), elicit signaling mechanisms that trigger immune responses in the hosts. Pathogen recognition receptors (PRRs) on the host cells recognize these PAMPs and initiate intracellular signaling through toll-like receptors (TLRs), RIG-I-like receptors (RLRs), and other pathways which induce production of pro-inflammatory cytokines and type I interferons. Recently, different members of tripartite motif containing proteins (TRIM) family of proteins were identified to intercept and regulate these cellular pathways. Specific targets of TRIM proteins have been identified and their molecular mechanisms were unraveled and identified unique domains involved in protein-protein interactions. Though innate immunity represents a tight and well conserved immune system in the host, gene expression in innate immunity was identified to be influenced by several epigenetic mechanisms including regulation by microRNAs (miRNAs). In this review, we present critical analysis of the findings on the identification of specific miRNAs that modulate expression of target genes involved in the regulation of innate immunity. Full article
Open AccessArticle
Development and Characterization of New Species Cross-Reactive Anti-Sialoadhesin Monoclonal Antibodies
Antibodies 2016, 5(2), 7; doi:10.3390/antib5020007 -
Abstract
Sialoadhesin (Sn) is a surface receptor expressed on a subset of macrophages in steady state conditions. During inflammation and diseases, Sn is highly upregulated on macrophages and blood monocytes. Therefore, therapies using monoclonal antibodies (mAbs) to target Sn-positive (Sn+) cells are
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Sialoadhesin (Sn) is a surface receptor expressed on a subset of macrophages in steady state conditions. During inflammation and diseases, Sn is highly upregulated on macrophages and blood monocytes. Therefore, therapies using monoclonal antibodies (mAbs) to target Sn-positive (Sn+) cells are a potential strategy for targeted treatment. It has been shown that Sn internalizes after binding with a mAb, though it is not clear whether this is species-specific. In this study, new Sn-specific mAbs were developed and analyzed for cross-reactivity between species. In addition, the newly developed mAbs were compared to mAbs used in previous research for their epitope recognition and other Sn-specific characteristics. Both species-specific and cross-reactive antibodies could be identified. Furthermore, sialic acid-binding of red blood cells (RBC) could be inhibited with mAbs recognizing different epitopes and all mAb showed internalization of Sn. The newly developed mAbs can be used as novel tools for Sn research and further analysis of Sn internalization in different species. Full article
Open AccessArticle
Development of PF-06671008, a Highly Potent Anti-P-cadherin/Anti-CD3 Bispecific DART Molecule with Extended Half-Life for the Treatment of Cancer
Antibodies 2016, 5(1), 6; doi:10.3390/antib5010006 -
Abstract
Bispecific antibodies offer a promising approach for the treatment of cancer but can be challenging to engineer and manufacture. Here we report the development of PF-06671008, an extended-half-life dual-affinity re-targeting (DART®) bispecific molecule against P-cadherin and CD3 that demonstrates antibody-like properties.
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Bispecific antibodies offer a promising approach for the treatment of cancer but can be challenging to engineer and manufacture. Here we report the development of PF-06671008, an extended-half-life dual-affinity re-targeting (DART®) bispecific molecule against P-cadherin and CD3 that demonstrates antibody-like properties. Using phage display, we identified anti-P-cadherin single chain Fv (scFv) that were subsequently affinity-optimized to picomolar affinity using stringent phage selection strategies, resulting in low picomolar potency in cytotoxic T lymphocyte (CTL) killing assays in the DART format. The crystal structure of this disulfide-constrained diabody shows that it forms a novel compact structure with the two antigen binding sites separated from each other by approximately 30 Å and facing approximately 90° apart. We show here that introduction of the human Fc domain in PF-06671008 has produced a molecule with an extended half-life (-4.4 days in human FcRn knock-in mice), high stability (Tm1 > 68 °C), high expression (>1 g/L), and robust purification properties (highly pure heterodimer), all with minimal impact on potency. Finally, we demonstrate in vivo anti-tumor efficacy in a human colorectal/human peripheral blood mononuclear cell (PBMC) co-mix xenograft mouse model. These results suggest PF-06671008 is a promising new bispecific for the treatment of patients with solid tumors expressing P-cadherin. Full article
Open AccessReview
Cytokines in the Germinal Center Niche
Antibodies 2016, 5(1), 5; doi:10.3390/antib5010005 -
Abstract
Cytokines are small, secreted, glycoproteins that specifically affect the interactions and communications between cells. Cytokines are produced transiently and locally, acting in a paracrine or autocrine manner, and they are extremely potent, ligating high affinity cell surface receptors to elicit changes in gene
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Cytokines are small, secreted, glycoproteins that specifically affect the interactions and communications between cells. Cytokines are produced transiently and locally, acting in a paracrine or autocrine manner, and they are extremely potent, ligating high affinity cell surface receptors to elicit changes in gene expression and protein synthesis in the responding cell. Cytokines produced during the differentiation of T follicular helper (Tfh) cells and B cells within the germinal center (GC) niche play an important role in ensuring that the humoral immune response is robust, whilst retaining flexibility, during the generation of affinity matured antibodies. Cytokines produced by B cells, antigen presenting cells and stromal cells are important for the differentiation of Tfh cells and Tfh cell produced cytokines act both in an autocrine fashion to firm Tfh cell differentiation and in a paracrine fashion to support the differentiation of memory B cells and plasma cells. In this review, we discuss the role of cytokines during the GC reaction with a particular focus on the influence of cytokines on Tfh cells. Full article
Open AccessEditorial
Acknowledgement to Reviewers of Antibodies in 2015
Antibodies 2016, 5(1), 4; doi:10.3390/antib5010004 -
Abstract The editors of Antibodies would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2015. [...] Full article
Open AccessReview
Anticytokine Autoantibodies: Association with Infection and Immune Dysregulation
Antibodies 2016, 5(1), 3; doi:10.3390/antib5010003 -
Abstract
The association of autoantibodies to cytokines with immune deficiency, autoimmunity and/or immune dysregulation is increasingly being recognized. For example, autoantibodies to interferon gamma have been found to be associated with chronic, treatment refractory infections with intracellular organisms such as mycobacteria, autoantibodies to interleukin
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The association of autoantibodies to cytokines with immune deficiency, autoimmunity and/or immune dysregulation is increasingly being recognized. For example, autoantibodies to interferon gamma have been found to be associated with chronic, treatment refractory infections with intracellular organisms such as mycobacteria, autoantibodies to interleukin 17 with chronic mucocutaneous candidiasis, and anti-interferon alpha autoantibodies with systemic lupus erythematosus. While low titer autoantibodies to these and other cytokines may be detected in normal individuals, patients with infectious or autoimmune manifestations tend to have high titer autoantibodies that may block or potentiate the function of the respective cytokine. Recognition of these autoantibodies is important because it may direct treatment toward a combination of adjunctive immunotherapy to modulate the autoantibody level while continuing with appropriate anti-microbial therapy. This review focuses on the anti-cytokine autoantibodies documented to date, their autoimmune, immune dysregulation and infectious disease associations, methods for detection of these antibodies and potential treatment options. Full article