Abstract:
:CD4(+) CD25(+) regulatory T cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the novel common gamma chain cytokine interleukin (IL)-21 on primary B cells from CLL patients. Since members of this family of cytokines are known to exhibit their effects on diverse immune cells, we have examined the effects of IL-21 on CLL patient derived regulatory T cell (Treg) induction, expansion and the inhibitory effect on natural killer cells in vitro. We demonstrate here the expression of IL-21 receptor in CD4(+)CD25(High) regulatory cells from CLL patients. In contrast to IL-2, the IL-21 cytokine failed to mediate expansion of regulatory T cells or induced expression of Foxp3 in CD4(+)CD25(Intermediate) or CD4(+)CD25(Dim/-) T cells in whole blood derived from CLL patients. Interestingly, in contrast to their differential effects on expansion of the CD4(+)CD25(+)Foxp3(+)T cells, IL-2 and IL-21 exhibited a redundant role in Treg mediated suppression of NK cell mediated antibody dependent cytotoxicity function. Given the infusion related toxicities and pro-survival effect of IL-2 in CLL, these studies provide a rationale to explore IL-21 as an alternate gamma chain cytokine in CLL therapy.
journal_name
MAbsjournal_title
mAbsauthors
Gowda A,Ramanunni A,Cheney C,Rozewski D,Kindsvogel W,Lehman A,Jarjoura D,Caligiuri M,Byrd JC,Muthusamy Ndoi
10.4161/mabs.2.1.10561subject
Has Abstractpub_date
2010-01-01 00:00:00pages
35-41issue
1eissn
1942-0862issn
1942-0870pii
10561journal_volume
2pub_type
杂志文章相关文献
mAbs文献大全abstract::Complex cellular targets such as G protein-coupled receptors (GPCRs), ion channels, and other multi-transmembrane proteins represent a significant challenge for therapeutic antibody discovery, primarily because of poor stability of the target protein upon extraction from cell membranes. To assess whether a limited set...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2020.1755069
更新日期:2020-01-01 00:00:00
abstract::Manipulation of binding affinity between monoclonal antibodies (mAbs) and the neonatal Fc receptor (FcRn) has been leveraged to extend mAb half-life; however, the steps required for success remain ambiguous and experimental observations are inconsistent. Recent models have considered the time course of endosomal trans...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2018.1506648
更新日期:2018-11-01 00:00:00
abstract::Fusion to an IgG Fc region is an established strategy to extend the half-life of therapeutic proteins. Most Fc fusion proteins, however, do not achieve the long half-life of IgGs. Based on findings that scFv-Fc fusion proteins exhibit a shorter half-life than the corresponding IgG molecules, we performed a comparative...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1113360
更新日期:2016-01-01 00:00:00
abstract::Process intensification has shown great potential to increase productivity and reduce costs in biomanufacturing. This case study describes the evolution of a manufacturing process from a conventional processing scheme at 1000-L scale (Process A, n = 5) to intensified processing schemes at both 1000-L (Process B, n = 8...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2020.1770669
更新日期:2020-01-01 00:00:00
abstract::Non-enzymatic glycation is a challenging post-translational modification to characterize due to the structural heterogeneity it generates in proteins. Glycation has become increasingly recognized as an important product quality attribute to monitor, particularly for the biotechnology sector, which produces recombinant...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1046663
更新日期:2015-01-01 00:00:00
abstract::Glycosylation is an important post-translational modification during protein production in eukaryotic cells, and it is essential for protein structure, stability, half-life, and biological functions. In this study, we produced various monoclonal antibody (mAb) glycoforms from Chinese hamster ovary (CHO) cells, includi...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.28588
更新日期:2014-05-01 00:00:00
abstract::We describe here the identification of a stop codon TAA (Stop) → GAA (Glu) = Stop221E mutation on the light chain of a recombinant IgG1 antibody expressed in a Chinese hamster ovary (CHO) cell line. The extended light chain variants, which were caused by translation beyond the mutated stop codon to the next alternativ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.22232
更新日期:2012-11-01 00:00:00
abstract::In recent years, capillary electrophoresis-sodium dodecyl sulfate (cSDS) has been widely used for high resolution separation and quantification of the fragments and aggregates of monoclonal antibodies (mAbs) to ensure the quality of mAb therapeutics. However, identification of the low-molecular-weight (LMW) and high-m...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2019.1646554
更新日期:2019-10-01 00:00:00
abstract::Highly concentrated antibody solutions often exhibit high viscosities, which present a number of challenges for antibody-drug development, manufacturing and administration. The antibody sequence is a key determinant for high viscosity of highly concentrated solutions; therefore, a sequence- or structure-based tool tha...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1099773
更新日期:2016-01-01 00:00:00
abstract::Monoclonal antibodies (mAb) have become a mainstay in tumor therapy. Clinical responses to mAb therapy, however, are far from optimal, with many patients presenting native or acquired resistance or suboptimal responses to a mAb therapy. MAbs exert antitumor activity through different mechanisms of action and we propos...
journal_title:mAbs
pub_type: 杂志文章,评审
doi:10.4161/mabs.22775
更新日期:2013-01-01 00:00:00
abstract::The Annual bioProcessUK Conference has acted as the key networking event for bioprocess scientists and engineers in the UK for the past 10 years. The following article is a report from the sessions that focused on continuous bioprocessing during the 10(th) Annual bioProcessUK Conference (London, December 2013). These ...
journal_title:mAbs
pub_type:
doi:10.4161/mabs.36151
更新日期:2014-01-01 00:00:00
abstract::We describe protein synthesis, folding and assembly of antibody fragments and full-length aglycosylated antibodies using an Escherichia coli-based open cell-free synthesis (OCFS) system. We use DNA template design and high throughput screening at microliter scale to rapidly optimize production of single-chain Fv (scFv...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.4.2.19202
更新日期:2012-03-01 00:00:00
abstract::Several angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway have been approved for cancer treatment. However, VEGF inhibitors alone were shown to promote tumor invasion and metastasis by increasing intratumoral hypoxia in some preclinical and clinical studies. Emerging rep...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2016.1171432
更新日期:2016-07-01 00:00:00
abstract::Ang1 is a soluble ligand to receptor Tie2, and increasing the circulating Ang1 level may improve vascular stabilization under certain disease conditions. Here, we found that the circulating Ang1 level was significantly increased in cynomolgus monkeys treated with non-neutralizing anti-Ang1 antibodies. Improving the an...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2018.1521130
更新日期:2018-11-01 00:00:00
abstract::Severe forms of dengue virus (DENV) infection frequently cause high case fatality rate. Currently, there is no effective vaccine against the infection. Clinical cases are given only palliative treatment as specific anti-DENV immunotherapy is not available and it is urgently required. In this study, human single-chain ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.27874
更新日期:2014-03-01 00:00:00
abstract::Although extensively studied, protein-protein interactions remain highly elusive and are of increasing interest in drug development. We show the assembly of a monoclonal antibody, using multivalent carboxylate ions, into highly-ordered structures. While the presence and function of similar structures in vivo are not k...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.23183
更新日期:2013-03-01 00:00:00
abstract::Antibodies are routinely used to study the activity of transcription factors, using various in vitro and in vivo approaches such as electrophoretic mobility shift assay, enzyme-linked immunosorbent assay, genome-wide method analysis coupled with next generation sequencing, or mass spectrometry. More recently, a new ap...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2018.1451288
更新日期:2018-05-01 00:00:00
abstract::Glycosylation is a critical attribute for development and manufacturing of therapeutic monoclonal antibodies (mAbs) in the pharmaceutical industry. Conventional antibody glycan analysis is usually achieved by the 2-aminobenzamide (2-AB) hydrophilic interaction liquid chromatography (HILIC) method following the release...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2016.1156828
更新日期:2016-05-01 00:00:00
abstract::An immunotoxin (IT) constructed with RFB4, a murine anti-CD22 monoclonal antibody, and the "deglycosylated" A chain of ricin has shown activity at safe doses in patients with non-Hodgkin lymphoma and in children with acute lymphoblastic leukemia. The dose limiting toxicity is vascular leak syndrome (VLS), which appear...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.4.1.18348
更新日期:2012-01-01 00:00:00
abstract::In the present study, we conducted a Phase 1 study of a recombinant anti-EGFR monoclonal antibody (CMAB009) that has the same amino acid sequence as cetuximab. The purpose of this study was to evaluate the safety, pharmacokinetics, and potential benefit of CMAB009 in Chinese patients with advanced chemotherapy-resista...
journal_title:mAbs
pub_type: 杂志文章,随机对照试验
doi:10.4161/mabs.3.1.14021
更新日期:2011-01-01 00:00:00
abstract::Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other t...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.25269
更新日期:2013-09-01 00:00:00
abstract::Monomeric IgA has been proposed as an alternative antibody format for cancer therapy. Here, we present our studies on the production, purification and functional evaluation of anti-HER2 IgA antibodies as anti-cancer agents in comparison to the anti-HER2 IgG1 trastuzumab. MALDI-TOF MS analysis showed profound differenc...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1102812
更新日期:2016-01-01 00:00:00
abstract::A costimulatory signal is required for the full activation of T cells, in addition to the antigen-specific signal via the T cell receptor. The inducible costimulator, ICOS is one of the costimulatory molecules that play an essential role in this process, particularly in the expansion or the development of effector T c...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.1.5.9633
更新日期:2009-09-01 00:00:00
abstract::Accurate measurement and functional characterization of antibody Fc domain N-linked glycans is critical to successful biosimilar development. Here, we describe the application of methods to accurately quantify and characterize the N-linked glycans of 2 IgG1 biosimilars with effector function activity, and show the pot...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1016692
更新日期:2015-01-01 00:00:00
abstract::MPDL3280A is a human monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1), and exerts anti-tumor activity mainly by blocking PD-L1 interaction with programmed cell death-1 (PD-1) and B7.1. It is being investigated as a potential therapy for locally advanced or metastatic malignancies. The purpose ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2015.1136043
更新日期:2016-01-01 00:00:00
abstract::The importance of the neonatal Fc receptor (FcRn) in extending the serum half-life of monoclonal antibodies (mAbs) is well demonstrated, and has led to the development of multiple engineering approaches designed to alter Fc interactions with FcRn. Recent reports have additionally highlighted the effect of nonspecific ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.1080/19420862.2016.1208330
更新日期:2016-10-01 00:00:00
abstract::The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling in endothelial and hematopoietic cells and thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn's role in the metabolism of IgG within individual tissu...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.28254
更新日期:2014-05-01 00:00:00
abstract::Genomic studies have been revolutionized by the use of next generation sequencing (NGS) that delivers huge amounts of sequence information in a short span of time. The number of applications for NGS is rapidly expanding and significantly transforming many areas of life sciences. The field of antibody research and disc...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.3.1.14169
更新日期:2011-01-01 00:00:00
abstract::There are currently ~25 recombinant full-length IgGs (rIgGs) in the market that have been approved by regulatory agencies as biotherapeutics to treat various human diseases. Most of these are based on IgG1k framework and are either chimeric, humanized or human antibodies manufactured using either Chinese hamster ovary...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.19868
更新日期:2012-05-01 00:00:00
abstract::During cell line development for an IgG1 antibody candidate (mAb1), a C-terminal extension was identified in 2 product candidate clones expressed in CHO-K1 cell line. The extension was initially observed as the presence of anomalous new peaks in these clones after analysis by cation exchange chromatography (CEX-HPLC) ...
journal_title:mAbs
pub_type: 杂志文章
doi:10.4161/mabs.36222
更新日期:2014-01-01 00:00:00