Comparing CDRH3 diversity captured from secondary lymphoid organs for the generation of recombinant human antibodies.

Abstract:

:The plasticity of natural immunoglobulin repertoires can be exploited for the generation of phage display libraries. Secondary lymphoid organs, such as the spleen and the lymph nodes, constitute interesting sources of diversity because they are rich in B cells, part of which can be affinity matured. These organs, however, differ in their anatomical structure, reflecting the different fluids they drain, which affects the B cell repertoires. The CDRH3 repertoires from these organs, extracted from naïve or immunized mice, were compared in the context of phage display libraries using human antibody framework families. Deep sequencing analysis revealed that all libraries displayed different CDRH3 repertoires, but the one derived from lymph nodes of naïve mice was the most diverse. Library performance was assessed by in vitro selection. For both organs, immunization increased substantially the frequency of molecules able to bind to the immunogen. The library derived from lymph nodes from naïve mice, however, was the most effective in generating diverse and high affinity candidates. These results illustrate that the use of a biased CDRH3 repertoire increases the performance of libraries, but reduces the clonal diversity, which may be detrimental for certain strategies.

journal_name

MAbs

journal_title

mAbs

authors

Venet S,Kosco-Vilbois M,Fischer N

doi

10.4161/mabs.25592

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

690-8

issue

5

eissn

1942-0862

issn

1942-0870

pii

25592

journal_volume

5

pub_type

杂志文章

相关文献

mAbs文献大全
  • Simultaneous blockade of VEGF and Dll4 by HD105, a bispecific antibody, inhibits tumor progression and angiogenesis.

    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

    authors: Lee D,Kim D,Choi YB,Kang K,Sung ES,Ahn JH,Goo J,Yeom DH,Jang HS,Moon KD,Lee SH,You WK

    更新日期:2016-07-01 00:00:00

  • Adsorption behavior of a human monoclonal antibody at hydrophilic and hydrophobic surfaces.

    abstract::One aspiration for the formulation of human monoclonal antibodies (mAb) is to reach high solution concentrations without compromising stability. Protein surface activity leading to instability is well known, but our understanding of mAb adsorption to the solid-liquid interface in relevant pH and surfactant conditions ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.22522

    authors: Couston RG,Skoda MW,Uddin S,van der Walle CF

    更新日期:2013-01-01 00:00:00

  • A human monoclonal antibody against small envelope protein of hepatitis B virus with potent neutralization effect.

    abstract::Hepatitis B virus (HBV) produces large (L), middle (M), and small (S) envelope proteins, alternatively referred to as hepatitis B surface antigen (HBsAg). Currently, yeast-derived S protein serves as the preventive vaccine, while hepatitis B immune globulin (HBIG) concentrated from pooled plasma of vaccine recipients ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2015.1134409

    authors: Wang W,Sun L,Li T,Ma Y,Li J,Liu Y,Li M,Wang L,Li C,Xie Y,Wen Y,Liang M,Chen L,Tong S

    更新日期:2016-01-01 00:00:00

  • A minimal physiologically based pharmacokinetic model to investigate FcRn-mediated monoclonal antibody salvage: Effects of Kon, Koff, endosome trafficking, and animal species.

    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

    authors: Maas BM,Cao Y

    更新日期:2018-11-01 00:00:00

  • Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

    abstract::Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched ...

    journal_title:mAbs

    pub_type: 杂志文章,评审

    doi:10.4161/mabs.3.5.16968

    authors: Munro TP,Mahler SM,Huang EP,Chin DY,Gray PP

    更新日期:2011-09-01 00:00:00

  • Development and validation of an LC-MS/MS method for simultaneous quantification of co-administered trastuzumab and pertuzumab.

    abstract::Given the increasing use of combination therapy with multiple monoclonal antibodies (mAbs), there is a clinical need for multiplexing assays. For the frequently co-administered anti-human epidermal growth factor receptor 2 (HER2) mAbs trastuzumab and pertuzumab, we developed a high-throughput and robust hybrid ligand-...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2020.1795492

    authors: Schokker S,Fusetti F,Bonardi F,Molenaar RJ,Mathôt RAA,van Laarhoven HWM

    更新日期:2020-01-01 00:00:00

  • Influence of glycosylation pattern on the molecular properties of monoclonal antibodies.

    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

    authors: Zheng K,Yarmarkovich M,Bantog C,Bayer R,Patapoff TW

    更新日期:2014-05-01 00:00:00

  • Antibody Fc engineering for enhanced neonatal Fc receptor binding and prolonged circulation half-life.

    abstract::The neonatal Fc receptor (FcRn) promotes antibody recycling through rescue from normal lysosomal degradation. The binding interaction is pH-dependent with high affinity at low pH, but not under physiological pH conditions. Here, we combined rational design and saturation mutagenesis to generate novel antibody variants...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2019.1633883

    authors: Mackness BC,Jaworski JA,Boudanova E,Park A,Valente D,Mauriac C,Pasquier O,Schmidt T,Kabiri M,Kandira A,Radošević K,Qiu H

    更新日期:2019-10-01 00:00:00

  • Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates.

    abstract::Antibody-drug conjugates (ADCs) represent a new class of cancer therapeutics. Their design involves a tumor-specific antibody, a linker and a cytotoxic payload. They were designed to allow specific targeting of highly potent cytotoxic agents to tumor cells whilst sparing normal cells. Frequent toxicities that may be d...

    journal_title:mAbs

    pub_type: 杂志文章,评审

    doi:10.1080/19420862.2016.1156829

    authors: Donaghy H

    更新日期:2016-05-01 00:00:00

  • Predicting Antibody Developability Profiles Through Early Stage Discovery Screening.

    abstract::Monoclonal antibodies play an increasingly important role for the development of new drugs across multiple therapy areas. The term 'developability' encompasses the feasibility of molecules to successfully progress from discovery to development via evaluation of their physicochemical properties. These properties includ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2020.1743053

    authors: Bailly M,Mieczkowski C,Juan V,Metwally E,Tomazela D,Baker J,Uchida M,Kofman E,Raoufi F,Motlagh S,Yu Y,Park J,Raghava S,Welsh J,Rauscher M,Raghunathan G,Hsieh M,Chen YL,Nguyen HT,Nguyen N,Cipriano D,Fayadat-Dilma

    更新日期:2020-01-01 00:00:00

  • Phase 1 study of anti-epidermal growth factor receptor monoclonal antibody in patients with solid tumors.

    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

    authors: Wang C,He X,Zhou B,Li J,Li B,Qian W,Hou S,Wang H,Shi Y,Guo Y

    更新日期:2011-01-01 00:00:00

  • Protein design of IgG/TCR chimeras for the co-expression of Fab-like moieties within bispecific antibodies.

    abstract::Immunoglobulins and T cell receptors (TCRs) share common sequences and structures. With the goal of creating novel bispecific antibodies (BsAbs), we generated chimeric molecules, denoted IgG_TCRs, where the Fv regions of several antibodies were fused to the constant domains of the α/β TCR. Replacing CH1 with Cα and CL...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2015.1007826

    authors: Wu X,Sereno AJ,Huang F,Zhang K,Batt M,Fitchett JR,He D,Rick HL,Conner EM,Demarest SJ

    更新日期:2015-01-01 00:00:00

  • Target-independent variable region mediated effects on antibody clearance can be FcRn independent.

    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

    authors: Kelly RL,Yu Y,Sun T,Caffry I,Lynaugh H,Brown M,Jain T,Xu Y,Wittrup KD

    更新日期:2016-10-01 00:00:00

  • Improved monovalent TNF receptor 1-selective inhibitor with novel heterodimerizing Fc.

    abstract::The development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment of inflammatory diseases has generated increasing interest. In particular, selective inhibition of TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only the pro-inflammatory r...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2019.1596512

    authors: Richter F,Seifert O,Herrmann A,Pfizenmaier K,Kontermann RE

    更新日期:2019-05-01 00:00:00

  • Red colored IgG4 caused by vitamin B12 from cell culture media combined with disulfide reduction at harvest.

    abstract::While many antibody therapeutics are formulated at low concentration (~10-20 mg/mL) for intravenous administration, high concentration (> 100 mg/mL) formulations may be required for subcutaneous delivery in certain clinical indications. For such high concentration formulations, product color is more apparent due to th...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.28257

    authors: Derfus GE,Dizon-Maspat J,Broddrick JT,Velayo AC,Toschi JD,Santuray RT,Hsu SK,Winter CM,Krishnan R,Amanullah A

    更新日期:2014-05-01 00:00:00

  • An optimized antibody-single-chain TRAIL fusion protein for cancer therapy.

    abstract::Fusion proteins combining oligomeric assemblies of a genetically obtained single-chain (sc) variant of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with antibodies directed against tumor-associated antigens represent a promising strategy to overcome the limited therapeutic activity of conventional s...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2016.1172163

    authors: Siegemund M,Seifert O,Zarani M,Džinić T,De Leo V,Göttsch D,Münkel S,Hutt M,Pfizenmaier K,Kontermann RE

    更新日期:2016-07-01 00:00:00

  • Functional domain analysis of SOX18 transcription factor using a single-chain variable fragment-based approach.

    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

    authors: Fontaine FR,Goodall S,Prokop JW,Howard CB,Moustaqil M,Kumble S,Rasicci DT,Osborne GW,Gambin Y,Sierecki E,Jones ML,Zuegg J,Mahler S,Francois M

    更新日期:2018-05-01 00:00:00

  • Utility of a human FcRn transgenic mouse model in drug discovery for early assessment and prediction of human pharmacokinetics of monoclonal antibodies.

    abstract::Therapeutic antibodies continue to develop as an emerging drug class, with a need for preclinical tools to better predict in vivo characteristics. Transgenic mice expressing human neonatal Fc receptor (hFcRn) have potential as a preclinical pharmacokinetic (PK) model to project human PK of monoclonal antibodies (mAbs)...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2016.1193660

    authors: Avery LB,Wang M,Kavosi MS,Joyce A,Kurz JC,Fan YY,Dowty ME,Zhang M,Zhang Y,Cheng A,Hua F,Jones HM,Neubert H,Polzer RJ,O'Hara DM

    更新日期:2016-08-01 00:00:00

  • Expression of antibodies using single open reading frame (sORF) vector design: Demonstration of manufacturing feasibility.

    abstract::Efficient production of large quantities of therapeutic antibodies is becoming a major goal of the pharmaceutical industry. We developed a proprietary expression system using a polyprotein precursor-based approach to antibody expression in mammalian cells. In this approach, the coding regions for heavy and light chain...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.25161

    authors: Gion WR,Davis-Taber RA,Regier DA,Fung E,Medina L,Santora LC,Bose S,Ivanov AV,Perilli-Palmer BA,Chumsae CM,Matuck JG,Kunes YZ,Carson GR

    更新日期:2013-07-01 00:00:00

  • A comparison of anti-HER2 IgA and IgG1 in vivo efficacy is facilitated by high N-glycan sialylation of the IgA.

    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

    authors: Rouwendal GJ,van der Lee MM,Meyer S,Reiding KR,Schouten J,de Roo G,Egging DF,Leusen JH,Boross P,Wuhrer M,Verheijden GF,Dokter WH,Timmers M,Ubink R

    更新日期:2016-01-01 00:00:00

  • Fluorescent Citrine-IgG fusion proteins produced in mammalian cells.

    abstract::Genetically encoded fluorescent antibodies are desirable for many applications in biotechnology, proteomics, microscopy, cell biology and molecular diagnostics, although efficient production of fluorescent IgGs in mammalian cells has been hampered by different and mutually incompatible secretion- and folding-requireme...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.2.6.13179

    authors: Haas AK,von Schwerin C,Matscheko D,Brinkmann U

    更新日期:2010-11-01 00:00:00

  • Improved in vitro and in vivo activity against CD303-expressing targets of the chimeric 122A2 antibody selected for specific glycosylation pattern.

    abstract::Plasmacytoid dendritic cells (pDCs) play a central role for both innate and adaptive antiviral responses, as they direct immune responses through their unique ability to produce substantial concentrations of type I interferon (IFNs) upon viral encounter while also activating multiple immune cells, including macrophage...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2018.1451283

    authors: Fournier N,Jacque E,Fontayne A,Derache D,Dupont G,Verhaeghe L,Baptista L,Dehenne A,Dezetter AS,Terrier A,Longue A,Pochet-Beghin V,Beghin C,Chtourou S,de Romeuf C

    更新日期:2018-05-01 00:00:00

  • High-throughput glycosylation analysis of therapeutic immunoglobulin G by capillary gel electrophoresis using a DNA analyzer.

    abstract::The Fc glycosylation of therapeutic antibodies is crucial for their effector functions and their behavior in pharmacokinetics and pharmacodynamics. To monitor the Fc glycosylation in bioprocess development and characterization,high-throughput techniques for glycosylation analysis are needed. Here, we describe the deve...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.26712

    authors: Reusch D,Haberger M,Kailich T,Heidenreich AK,Kampe M,Bulau P,Wuhrer M

    更新日期:2014-01-01 00:00:00

  • Immunotherapy for Alzheimer disease.

    abstract::Immunotherapy approaches for Alzheimer disease currently are among the leading therapeutic directions for the disease. Active and passive immunotherapy against the beta-amyloid peptides that aggregate and accumulate in the brain of those afflicted by the disease have been shown by numerous groups to reduce plaque path...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.1.2.7829

    authors: Gouras GK

    更新日期:2009-03-01 00:00:00

  • Galactosylation variations in marketed therapeutic antibodies.

    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

    authors: Raju TS,Jordan RE

    更新日期:2012-05-01 00:00:00

  • Investigation of the effect of salt additives in Protein L affinity chromatography for the purification of tandem single-chain variable fragment bispecific antibodies.

    abstract::Tandem single-chain variable fragment (scFv) bispecific antibodies (bsAb) are one of the most promising bsAb formats reported thus far. Yet, because of their increased aggregation propensity, high impurity content due to low expression level, smaller size and lack of the Fc region, it is challenging to isolate these p...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2020.1718440

    authors: Chen SW,Tan D,Yang YS,Zhang W

    更新日期:2020-01-01 00:00:00

  • In vitro and in vivo modifications of recombinant and human IgG antibodies.

    abstract::Tremendous knowledge has been gained in the understanding of various modifications of IgG antibodies, driven mainly by the fact that antibodies are one of the most important groups of therapeutic molecules and because of the development of advanced analytical techniques. Recombinant monoclonal antibody (mAb) therapeut...

    journal_title:mAbs

    pub_type: 杂志文章,评审

    doi:10.4161/mabs.29883

    authors: Liu H,Ponniah G,Zhang HM,Nowak C,Neill A,Gonzalez-Lopez N,Patel R,Cheng G,Kita AZ,Andrien B

    更新日期:2014-01-01 00:00:00

  • Continuous bioprocessing: the real thing this time? 10(th) Annual bioProcessUK Conference, December 3-4, 2013, London, UK.

    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

    authors: Farid SS,Thompson B,Davidson A

    更新日期:2014-01-01 00:00:00

  • Site-specific antibody-drug conjugate heterogeneity characterization and heterogeneity root cause analysis.

    abstract::Site-specific antibody-drug conjugates (ADCs) are designed to overcome the heterogeneity observed with first-generation ADCs that use random conjugation to surface-exposed lysine residues or conjugation to interchain disulfide bonds. Despite significantly enhanced homogeneity, however, the production of site-specific ...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.1080/19420862.2019.1624127

    authors: Cao M,De Mel N,Jiao Y,Howard J,Parthemore C,Korman S,Thompson C,Wendeler M,Liu D

    更新日期:2019-08-01 00:00:00

  • Rational identification of an optimal antibody mixture for targeting the epidermal growth factor receptor.

    abstract::The epidermal growth factor receptor (EGFR) is frequently dysregulated in human malignancies and a validated target for cancer therapy. Two monoclonal anti-EGFR antibodies (cetuximab and panitumumab) are approved for clinical use. However, the percentage of patients responding to treatment is low and many patients exp...

    journal_title:mAbs

    pub_type: 杂志文章

    doi:10.4161/mabs.3.6.17955

    authors: Koefoed K,Steinaa L,Søderberg JN,Kjær I,Jacobsen HJ,Meijer PJ,Haurum JS,Jensen A,Kragh M,Andersen PS,Pedersen MW

    更新日期:2011-11-01 00:00:00