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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Marc Berger (Creator)
Tracey Bonfield (Creator)
Qimin Chao (Creator)
Diane Davidson (Creator)
Gaurav Deshmukh (Creator)
Brian Drozdowski (Creator)
Wolfgang Ebel (Creator)
Luigi Grasso (Creator)
Stephen Harley (Creator)
Marianne Henry (Creator)
Sara Jacob (Creator)
Mani Kavuru (Creator)
Brad Kline (Creator)
Ella Lazo (Creator)
Jian Li (Creator)
Nicholas C. Nicolaides (Creator)
Frank Rotella (Creator)
Eric Routhier (Creator)
Kathryn Rudolph (Creator)
Jeaneen Sage (Creator)
Tao Sai (Creator)
Philip M. Sass (Creator)
Paul Simon (Creator)
Mary Jane Thomassen (Creator)
Jun Yao (Creator)
Yuhong Zhou (Creator)
East Carolina University (ECU )
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Abstract: Current strategies for the production of therapeutic mAbs include he use of mammalian cell systems to recombinantly produce Abs erived from mice bearing human Ig transgenes humanization of odent Abs or phage libraries. Generation of hybridomas secreting uman mAbs has been previously reported; however this approach as not been fully exploited for immunotherapy development. e previously reported the use of transient regulation of ellular DNA mismatch repair processes to enhance traits (e.g. ffinity and titers) of mAb-producing cell lines including hybridomas. e reasoned that this process named morphogenics could e used to improve suboptimal hybridoma cells generated by eans of ex vivo immunization and immortalization of antigenspecific uman B cells for therapeutic Ab development. Here we resent a platform process that combines hybridoma and morphogenics echnologies for the generation of fully human mAbs pecific for disease-associated human antigens. We were able to enerate hybridoma lines secreting mAbs with high binding specificity nd biological activity. One mAb with strong neutralizing ctivity against human granulocyte–macrophage colony-stimulating actor was identified that is now considered for preclinical evelopment for autoimmune disease indications. Moreover hese hybridoma cells have proven suitable for genetic optimization sing the morphogenics process and have shown potential for arge-scale manufacturing. Originally published Proceedings of the National Academy of Sciences Vol. 103 No. 10 Mar 2006

Additional Information

Proceedings of the National Academy of Sciences. 103:10(March 2006) p. 3557-3562.
Language: English
Date: 2011
morphogenics, therapeutic antibody

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