About: Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle

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About: Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle
Creator	Sullivan, Eddie Wu, Hua Kasinathan, Poothappillai Kuroiwa, Yoshimi Sano, Akiko Wang, Zhongde Jiao, Jin-An Co-, Hiroaki Falls, Sioux Health, Sanford Jiao, Eddie Matsushita, Matsushita, Hua South, Dakota Sullivan, Wu, Jin-An
Source	Medline; PMC
abstract	Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.
has issue date	2013-10-24(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0078119
bibo:pmid	24205120
has license	cc-by
sha1sum (hex)	bdfce208ef62424bc68fdb610364dab6416365e1
schema:url	https://doi.org/10.1371/journal.pone.0078119
resource representing a document's title	Physiological Level Production of Antigen-Specific Human Immunoglobulin in Cloned Transchromosomic Cattle
has PubMed Central identifier	PMC3813428
has PubMed identifier	24205120
schema:publication	PLoS One
resource representing a document's body	covid:bdfce208ef62424bc68fdb610364dab6416365e1#body_text
is schema:about of	named entity 'CATTLE' named entity 'POOLED' named entity 'PROLIFERATION' named entity 'THESE' named entity 'HEAVY' named entity 'VIRUSES' named entity 'CATTLE' named entity 'DOMAIN' named entity 'INTERACTION' named entity 'TREATMENT' named entity 'IMMUNIZATION' named entity 'EFFECTIVE' named entity 'PHYSIOLOGICAL LEVEL' named entity 'HUMAN DISEASES' named entity 'INVOLVED' named entity 'INCOMPATIBILITY' named entity 'APPROVED' named entity 'OVERALL' named entity 'DIVERSITY' named entity 'BIG' named entity 'FUNCTIONALITY' named entity 'FOOD AND DRUG ADMINISTRATION' named entity 'HIGH LEVEL' named entity 'REPORT' named entity 'HUMAN IMMUNOGLOBULIN' named entity 'DERIVED' named entity 'B CELL ACTIVATION' named entity 'HIGH' named entity 'PLASMA' named entity 'HUMAN IGG' named entity 'HUMAN IMMUNOGLOBULIN' named entity 'ANTIGEN' named entity 'IMPROVEMENT' named entity 'LYMPHOCYTE DEVELOPMENT' named entity 'BCR' named entity 'IMMUNOGLOBULIN' named entity 'HUMAN' named entity 'POWERED' named entity 'SPECIFIC' named entity 'TUMOR' named entity 'DONORS' named entity 'CLONED' named entity 'PRODUCTION' named entity 'SPECIFIC' named entity 'ENTIRE' named entity 'IGM' named entity 'GERMLINE' named entity 'REPLACED' named entity 'EVOLVING' named entity 'HAC' named entity 'HEAVY-CHAIN' named entity 'INACTIVATED' named entity 'CAUSED BY' named entity 'PRE-B CELL RECEPTOR' named entity 'PARTIALLY' named entity 'HUMAN ARTIFICIAL CHROMOSOME' named entity 'TRANSMEMBRANE' named entity 'THERAPEUTIC' named entity 'SUCCESSFUL' named entity 'LOCI' named entity 'BOVINE' named entity 'IMMUNOGLOBULINS' named entity 'PROTEIN ' named entity 'CHAINS' named entity 'PREVIOUSLY' named entity 'HIGM'

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