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Human antibodies for immunotherapy development generated via a human B‐cell hybridoma technology
Author(s) -
LI JIAN,
Sai Tao,
Berger Marc,
Chao Qimin,
Davidson Diane,
Deshmukh Gaurav,
Drozdowski Brian,
Ebel Wolfgang,
Harley Stephen,
Henry Marianne,
Kline Brad,
Lazo Ella,
Rotella Frank,
Rudolf Kathryn,
Sage Jeaneen,
Simon Paul,
Yao Jun,
Zhou Yuhong,
Kavuru Mani,
Bonfield Tracey,
Thomassen Mary J.,
Sass Philip,
Nicolaides Nicholas,
Grasso Luigi
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb110
Subject(s) - monoclonal antibody , hybridoma technology , antibody , immunotherapy , antigen , transgene , ex vivo , biology , cell culture , recombinant dna , phage display , immunology , virology , computational biology , microbiology and biotechnology , in vivo , immune system , gene , genetics
Current strategies for the production of therapeutic MAbs include the use of mammalian cell systems to recombinantly produce antibodies derived from mice bearing human immunoglobulin transgenes, humanization of rodent antibodies, or phage libraries. We have previously reported the use of transient regulation of cellular DNA mismatch repair processes to enhance traits (e.g. affinity, titers) of MAb‐producing cell lines, including hybridomas. We reasoned that this process, named morphogenics, could be utilized to improve suboptimal hybridoma cells generated via ex‐vivo immunization and immortalization of antigen‐specific human B‐cells for therapeutic antibodies 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 GM‐CSF was identified that is currently advanced to 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.