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Human antibodies for immunotherapy development generated via a human B cell hybridoma technology

dc.contributor.authorLi, Jianen_US
dc.contributor.authorSai, Taoen_US
dc.contributor.authorBerger, Marcen_US
dc.contributor.authorChao, Qiminen_US
dc.contributor.authorDavidson, Dianeen_US
dc.contributor.authorDeshmukh, Gauraven_US
dc.contributor.authorDrozdowski, Brianen_US
dc.contributor.authorEbel, Wolfgangen_US
dc.contributor.authorHarley, Stephenen_US
dc.contributor.authorHenry, Marianneen_US
dc.contributor.authorJacob, Saraen_US
dc.contributor.authorKline, Braden_US
dc.contributor.authorLazo, Ellaen_US
dc.contributor.authorRotella, Franken_US
dc.contributor.authorRouthier, Ericen_US
dc.contributor.authorRudolph, Kathrynen_US
dc.contributor.authorSage, Jeaneenen_US
dc.contributor.authorSimon, Paulen_US
dc.contributor.authorYao, Junen_US
dc.contributor.authorZhou, Yuhongen_US
dc.contributor.authorKavuru, Mani S.en_US
dc.contributor.authorBonfield, Tracey L.en_US
dc.contributor.authorThomassen, Mary Janeen_US
dc.contributor.authorSass, Philip M.en_US
dc.contributor.authorNicolaides, Nicholas C.en_US
dc.contributor.authorGrasso, Luigien_US
dc.date.accessioned2011-04-15T16:41:21Zen_US
dc.date.accessioned2011-05-17T01:07:44Z
dc.date.available2011-04-15T16:41:21Zen_US
dc.date.available2011-05-17T01:07:44Z
dc.date.issued2006-03-07en_US
dc.description.abstractCurrent strategies for the production of therapeutic mAbs include the use of mammalian cell systems to recombinantly produce Abs derived from mice bearing human Ig transgenes, humanization of rodent Abs, or phage libraries. Generation of hybridomas secreting human mAbs has been previously reported; however, this approach has not been fully exploited for immunotherapy development. We previously reported the use of transient regulation of cellular DNA mismatch repair processes to enhance traits (e.g., affinity and titers) of mAb-producing cell lines, including hybridomas. We reasoned that this process, named morphogenics, could be used to improve suboptimal hybridoma cells generated by means of ex vivo immunization and immortalization of antigenspecific human B cells for therapeutic Ab development. Here we present a platform process that combines hybridoma and morphogenics technologies for the generation of fully human mAbs specific for disease-associated human antigens. We were able to generate hybridoma lines secreting mAbs with high binding specificity and biological activity. One mAb with strong neutralizing activity against human granulocyte–macrophage colony-stimulating factor was identified that is now considered for preclinical development for autoimmune disease indications. Moreover, these hybridoma cells have proven suitable for genetic optimization using the morphogenics process and have shown potential for large-scale manufacturing. Originally published Proceedings of the National Academy of Sciences, Vol. 103, No. 10, Mar 2006en_US
dc.identifier.citationProceedings of the National Academy of Sciences; 103:10 p. 3557-3562en_US
dc.identifier.doi10.1073/pnas.0511285103
dc.identifier.pmidPMC1383494en_US
dc.identifier.urihttp://hdl.handle.net/10342/3343en_US
dc.language.isoen_USen_US
dc.publisherEast Carolina Universityen_US
dc.relation.urihttp://www.pnas.org/content/by/year/2006en_US
dc.rightsAuthor notified of opt-out rights by Cammie Jennings prior to upload of this article.en_US
dc.subjectMorphogenicsen_US
dc.subjectTherapeutic antibodyen_US
dc.titleHuman antibodies for immunotherapy development generated via a human B cell hybridoma technologyen_US
dc.typeArticleen_US
ecu.journal.issue10
ecu.journal.nameProceedings of the National Academy of Sciences
ecu.journal.pages3557-3562
ecu.journal.volume103

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