Multispecific Antibody Development Platform Based on Human Heavy Chain Antibodies.


:Heavy chain-only antibodies (HCAbs) do not associate with light chains and their VH regions are functional as single domains, forming the smallest active antibody fragment. These VH regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules and may also be attached in series to construct multispecific antibodies without the need for protein engineering to ensure proper heavy and light chain pairing. Production of human HCAbs has been impeded by the fact that natural human VH regions require light chain association and display poor biophysical characteristics when expressed in the absence of light chains. Here, we present an innovative platform for the rapid development of diverse sets of human HCAbs that have been selected in vivo. Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human VH domains in response to an antigen challenge. UniRats express HCAbs from large transgenic loci representing the entire productive human heavy chain V(D)J repertoire, mount robust immune responses to a wide array of antigens, exhibit diverse V gene usage and generate large panels of stable, high affinity, antigen-specific molecules.


Front Immunol


Frontiers in immunology


Clarke SC,Ma B,Trinklein ND,Schellenberger U,Osborn MJ,Ouisse LH,Boudreau A,Davison LM,Harris KE,Ugamraj HS,Balasubramani A,Dang KH,Jorgensen B,Ogana HAN,Pham DT,Pratap PP,Sankaran P,Anegon I,van Schooten WC,Brüggem




Has Abstract


2019-01-07 00:00:00








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    abstract::CD27 expression has been used to distinguish between memory and naive B cells in humans. However, low levels of mutated and isotype-switched CD27-IgD- cells are seen in healthy adults, and these are increased in some autoimmune diseases and in the elderly. Thus CD27 is not a universal marker of memory B cells in human...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Wu YC,Kipling D,Dunn-Walters DK

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  • The NF-κB Signaling Pathway, the Microbiota, and Gastrointestinal Tumorigenesis: Recent Advances.

    abstract::Gastrointestinal (GI) cancers, especially gastric cancer and colorectal cancer (CRC), represent a major global health burden. A large population of microorganisms residing in the GI tract regulate physiological processes, such as the immune response, metabolic balance, and homeostasis. Accumulating evidence has reveal...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Peng C,Ouyang Y,Lu N,Li N

    更新日期:2020-06-30 00:00:00

  • Umbilical Cord Blood Natural Killer Cells, Their Characteristics, and Potential Clinical Applications.

    abstract::Natural killer (NK) cells are lymphocytes of the innate immune system able to kill different targets such as cancer cells and virally infected cells without prior activation making then attractive candidates for cancer immunotherapy. Umbilical cord blood (UCB) has become a source of hematopoietic stem cells for transp...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Sarvaria A,Jawdat D,Madrigal JA,Saudemont A

    更新日期:2017-03-23 00:00:00

  • Wide Cytokine Analysis in Cerebrospinal Fluid at Diagnosis Identified CCL-3 as a Possible Prognostic Factor for Multiple Sclerosis.

    abstract::Background: Apart from IgG oligoclonal bands, no other biomarker has, to date, been validated for diagnostic and/or prognostic purposes in multiple sclerosis (MS). Aim: To investigate a wide panel of cytokines and chemokines in the cerebrospinal fluid (CSF) of relapsing-remitting MS (RRMS) patients and evaluate their ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Puthenparampil M,Stropparo E,Zywicki S,Bovis F,Cazzola C,Federle L,Grassivaro F,Rinaldi F,Perini P,Sormani MP,Gallo P

    更新日期:2020-03-05 00:00:00

  • Reduction and Functional Exhaustion of T Cells in Patients With Coronavirus Disease 2019 (COVID-19).

    abstract::Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Diao B,Wang C,Tan Y,Chen X,Liu Y,Ning L,Chen L,Li M,Liu Y,Wang G,Yuan Z,Feng Z,Zhang Y,Wu Y,Chen Y

    更新日期:2020-05-01 00:00:00

  • What Is the Clinical Relevance of TNF Inhibitor Immunogenicity in the Management of Patients With Rheumatoid Arthritis?

    abstract::Tumor necrosis factor-α inhibitors (TNFis) have revolutionized the management of rheumatoid arthritis (RA), however despite considerable progress, only a small proportion of patients maintain long-term clinical response. Selection of, and switching between, biologics is mainly empirical, experiential, and not evidence...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Mehta P,Manson JJ

    更新日期:2020-04-07 00:00:00

  • Exploitation of Neisseria meningitidis Group B OMV Vaccines Against N. gonorrhoeae to Inform the Development and Deployment of Effective Gonorrhea Vaccines.

    abstract::Have potential clues to an effective gonorrhea vaccine been lurking in international disease surveillance data for decades? While no clinically effective vaccines against gonorrhea have been developed we present direct and indirect evidence that a vaccine is not only possible, but may already exist. Experience from Cu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Petousis-Harris H,Radcliff FJ

    更新日期:2019-04-09 00:00:00

  • Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT.

    abstract::Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Nove...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Mammadli M,Huang W,Harris R,Sultana A,Cheng Y,Tong W,Pu J,Gentile T,Dsouza S,Yang Q,Bah A,August A,Karimi M

    更新日期:2020-11-26 00:00:00

  • Are Mast Cells MASTers in Cancer?

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Varricchi G,Galdiero MR,Loffredo S,Marone G,Iannone R,Marone G,Granata F

    更新日期:2017-04-12 00:00:00

  • Human β-Defensin 2 Mediated Immune Modulation as Treatment for Experimental Colitis.

    abstract::Defensins represents an integral part of the innate immune system serving to ward off potential pathogens and to protect the intestinal barrier from microbial encroachment. In addition to their antimicrobial activities, defensins in general, and human β-defensin 2 (hBD2) in particular, also exhibit immunomodulatory ca...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Koeninger L,Armbruster NS,Brinch KS,Kjaerulf S,Andersen B,Langnau C,Autenrieth SE,Schneidawind D,Stange EF,Malek NP,Nordkild P,Jensen BAH,Wehkamp J

    更新日期:2020-01-31 00:00:00

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    abstract::Understanding the mechanisms of human immunodeficiency virus type I (HIV-1) pathogenesis would facilitate the identification of new therapeutic targets to control the infection in face of current antiretroviral therapy limitations. CD74 membrane expression is upregulated in HIV-1-infected cells and the magnitude of it...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Trifone C,Salido J,Ruiz MJ,Leng L,Quiroga MF,Salomón H,Bucala R,Ghiglione Y,Turk G

    更新日期:2018-06-27 00:00:00

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Andrieu JM,Chen S,Lai C,Guo W,Lu W

    更新日期:2014-06-30 00:00:00

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Takamura S,Kohlmeier JE

    更新日期:2019-04-05 00:00:00

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Zipfel PF,Wiech T,Rudnick R,Afonso S,Person F,Skerka C

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Frost EL,Lukacher AE

    更新日期:2015-01-05 00:00:00

  • Clinical Relevance of Galectin-1 and Galectin-3 in Rheumatoid Arthritis Patients: Differential Regulation and Correlation With Disease Activity.

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    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Mendez-Huergo SP,Hockl PF,Stupirski JC,Maller SM,Morosi LG,Pinto NA,Berón AM,Musuruana JL,Nasswetter GG,Cavallasca JA,Rabinovich GA

    更新日期:2019-01-09 00:00:00

  • White Spot Syndrome Virus-Induced Shrimp miR-315 Attenuates Prophenoloxidase Activation via PPAE3 Gene Suppression.

    abstract::MicroRNAs (miRNAs), the small non-coding RNAs, play a pivotal role in post-transcriptional gene regulation in various cellular processes. However, the miRNA function in shrimp antiviral response is not clearly understood. This research aims to uncover the function of pmo-miR-315, a white spot syndrome virus (WSSV)-res...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Jaree P,Wongdontri C,Somboonwiwat K

    更新日期:2018-09-25 00:00:00

  • Age-Based Dynamics of a Stable Circulating Cd8 T Cell Repertoire Component.

    abstract::T-cell memory to pathogens can be envisioned as a receptor-based imprint of the pathogenic environment on the naïve repertoire of clonotypes. Recurrent exposures to a pathogen inform and reinforce memory, leading to a mature state. The complexity and temporal stability of this system in man is only beginning to be ade...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Naumova EN,Yassai MB,Demos W,Reed E,Unruh M,Haribhai D,Williams CB,Naumov YN,Gorski J

    更新日期:2019-08-06 00:00:00

  • Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts.

    abstract::Borrelia burgdorferi sensu lato species complex is capable of establishing persistent infections in a wide variety of species, particularly rodents. Infection is asymptomatic or mild in most reservoir host species, indicating successful co-evolution of the pathogen with its natural hosts. However, infected humans and ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Tracy KE,Baumgarth N

    更新日期:2017-02-20 00:00:00

  • Hypomorphic Mutations in the BCR Signalosome Lead to Selective Immunoglobulin M Deficiency and Impaired B-cell Homeostasis.

    abstract::B cell activation via the B cell receptor (BCR) signalosome involves participation of signaling molecules such as BTK and BLNK. Genetic defects in these molecules are known to impair B cell differentiation and subsequently lead to agammaglobulinemia. Here we identified novel mutations in BTK and BLNK in two unrelated ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Geier CB,Sauerwein KMT,Leiss-Piller A,Zmek I,Fischer MB,Eibl MM,Wolf HM

    更新日期:2018-12-18 00:00:00

  • Pharmacological Inhibition of Amyloidogenic APP Processing and Knock-Down of APP in Primary Human Macrophages Impairs the Secretion of Cytokines.

    abstract::It has been previously shown that the amyloid precursor protein (APP) support the innate immune defense as an immune receptor. Amyloid β (Aβ) peptides seem to have properties of an antimicrobial peptide and can act as opsonines. In APP-deficient mouse models, a reduced secretion of cytokines has been observed. Still, ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Spitzer P,Walter M,Göth C,Oberstein TJ,Linning P,Knölker HJ,Kornhuber J,Maler JM

    更新日期:2020-09-03 00:00:00

  • The Small GTPase Rab5c Exerts Bi-Function in Singapore Grouper Iridovirus Infections and Cellular Responses in the Grouper, Epinephelus coioides.

    abstract::The small GTPase Rab5 is one of the master regulators of vesicular trafficking that participates in early stages of the endocytic pathway, such as endocytosis and endosome maturation. Three Rab5 isoforms (a, b, and c) share high sequence identity, and exhibit complex functions. However, the role of Rab5c in virus infe...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Wang L,Li C,Zhang X,Yang M,Wei S,Huang Y,Qin Q,Wang S

    更新日期:2020-09-02 00:00:00

  • Neuroimmunology of Behavioral Comorbidities Associated With Cancer and Cancer Treatments.

    abstract::Behavioral comorbidities (depression, anxiety, fatigue, cognitive disturbances, and neuropathic pain) are prevalent in cancer patients and survivors. These mental and neurological health issues reduce quality-of-life, which is a significant societal concern given the increasing rates of long-term survival after variou...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Santos JC,Pyter LM

    更新日期:2018-06-07 00:00:00

  • Granulocytes: New Members of the Antigen-Presenting Cell Family.

    abstract::Granulocytes, the most abundant types of leukocytes, are the first line of defense against pathogen invasion. However, the plasticity and diversity of granulocytes have been increasingly revealed, especially with regard to their versatile functions in orchestrating adaptive immune responses. A substantial body of rece...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Lin A,Loré K

    更新日期:2017-12-11 00:00:00

  • Sex Bias in Asthma Prevalence and Pathogenesis.

    abstract::Sex-related differences in asthma prevalence are well established and change through the reproductive phases of life. As children, boys have increased prevalence of asthma compared to girls. However, as adults, women have increased prevalence of asthma compared to men. Many factors, including genetics, environment, im...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Shah R,Newcomb DC

    更新日期:2018-12-18 00:00:00

  • Dysregulated TRAF3 and BCL2 Expression Promotes Multiple Classes of Mature Non-hodgkin B Cell Lymphoma in Mice.

    abstract::TNF-Receptor Associated Factor (TRAF)-3 is a master regulator of B cell homeostasis and function. TRAF3 has been shown to bind and regulate various proteins involved in the control of innate and adaptive immune responses. Previous studies showed that TRAF3 overexpression renders B cells hyper-reactive to antigens and ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Perez-Chacon G,Adrados M,Vallejo-Cremades MT,Lefebvre S,Reed JC,Zapata JM

    更新日期:2019-01-11 00:00:00

  • Respiratory Disease following Viral Lung Infection Alters the Murine Gut Microbiota.

    abstract::Alterations in the composition of the gut microbiota have profound effects on human health. Consequently, there is great interest in identifying, characterizing, and understanding factors that initiate these changes. Despite their high prevalence, studies have only recently begun to investigate how viral lung infectio...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Groves HT,Cuthbertson L,James P,Moffatt MF,Cox MJ,Tregoning JS

    更新日期:2018-02-12 00:00:00

  • Distinguishing Sepsis From Infection by Neutrophil Dysfunction: A Promising Role of CXCR2 Surface Level.

    abstract::Sepsis is one of the well-established diseases with specific patterns of neutrophil dysfunctions. Previous studies demonstrated sepsis-related neutrophil dysfunctions in comparison with subjects without infection. Since sepsis and infection are recently recognized as distinctive processes, whether these neutrophil dys...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: Seree-Aphinan C,Vichitkunakorn P,Navakanitworakul R,Khwannimit B

    更新日期:2020-12-23 00:00:00

  • NOD-Like Receptors in Lung Diseases.

    abstract::The lung is a particularly vulnerable organ at the interface of the body and the exterior environment. It is constantly exposed to microbes and particles by inhalation. The innate immune system needs to react promptly and adequately to potential dangers posed by these microbes and particles, while at the same time avo...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审


    authors: Chaput C,Sander LE,Suttorp N,Opitz B

    更新日期:2013-11-21 00:00:00

  • Negative Effect of Age, but Not of Latent Cytomegalovirus Infection on the Antibody Response to a Novel Influenza Vaccine Strain in Healthy Adults.

    abstract::Older adults are more vulnerable to influenza virus infection and at higher risk for severe complications and influenza-related death compared to younger adults. Unfortunately, influenza vaccine responses tend to be impaired in older adults due to aging of the immune system (immunosenescence). Latent infection with cy...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章


    authors: van den Berg SPH,Wong A,Hendriks M,Jacobi RHJ,van Baarle D,van Beek J

    更新日期:2018-01-29 00:00:00