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

Abstract

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.