Human antibodies for immunotherapy development generated via a human B cell hybridoma technology
Li, Jian; Sai, Tao; Berger, Marc; Chao, Qimin; Davidson, Diane; Deshmukh, Gaurav; Drozdowski, Brian; Ebel, Wolfgang; Harley, Stephen; Henry, Marianne; Jacob, Sara; Kline, Brad; Lazo, Ella; Rotella, Frank; Routhier, Eric; Rudolph, Kathryn; Sage, Jeaneen; Simon, Paul; Yao, Jun; Zhou, Yuhong; Kavuru, Mani; Bonfield, Tracey L.; Thomassen, Mary Jane; Sass, Philip M.; Nicolaides, Nicholas C.; Grasso, Luigi
Current 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 2006
Li, Jian, & Sai, Tao, & Berger, Marc, & Chao, Qimin, & Davidson, Diane, & Deshmukh, Gaurav, & Drozdowski, Brian, & Ebel, Wolfgang, & Harley, Stephen, & Henry, Marianne, & Jacob, Sara, & Kline, Brad, & Lazo, Ella, & Rotella, Frank, & Routhier, Eric, & Rudolph, Kathryn, & Sage, Jeaneen, & Simon, Paul, & Yao, Jun, & Zhou, Yuhong, & Kavuru, Mani, & Bonfield, Tracey L., & Thomassen, Mary Jane, & Sass, Philip M., & Nicolaides, Nicholas C., & Grasso, Luigi. (March 2006). Human antibodies for immunotherapy development generated via a human B cell hybridoma technology. Proceedings of the National Academy of Sciences, 103(10), 3557- 3562. Retrieved from http://hdl.handle.net/10342/3343
Li, Jian, and Sai, Tao, and Berger, Marc, and Chao, Qimin, and Davidson, Diane, and Deshmukh, Gaurav, and Drozdowski, Brian, and Ebel, Wolfgang, and Harley, Stephen, and Henry, Marianne, and Jacob, Sara, and Kline, Brad, and Lazo, Ella, and Rotella, Frank, and Routhier, Eric, and Rudolph, Kathryn, and Sage, Jeaneen, and Simon, Paul, and Yao, Jun, and Zhou, Yuhong, and Kavuru, Mani, and Bonfield, Tracey L., and Thomassen, Mary Jane, and Sass, Philip M., and Nicolaides, Nicholas C., and Grasso, Luigi. "Human antibodies for immunotherapy development generated via a human B cell hybridoma technology". Proceedings of the National Academy of Sciences. 103:10. (3557-3562), March 2006. January 16, 2019. http://hdl.handle.net/10342/3343.
Li, Jian and Sai, Tao and Berger, Marc and Chao, Qimin and Davidson, Diane and Deshmukh, Gaurav and Drozdowski, Brian and Ebel, Wolfgang and Harley, Stephen and Henry, Marianne and Jacob, Sara and Kline, Brad and Lazo, Ella and Rotella, Frank and Routhier, Eric and Rudolph, Kathryn and Sage, Jeaneen and Simon, Paul and Yao, Jun and Zhou, Yuhong and Kavuru, Mani and Bonfield, Tracey L. and Thomassen, Mary Jane and Sass, Philip M. and Nicolaides, Nicholas C. and Grasso, Luigi, "Human antibodies for immunotherapy development generated via a human B cell hybridoma technology," Proceedings of the National Academy of Sciences 103, no. 10 (March 2006), http://hdl.handle.net/10342/3343 (accessed January 16, 2019).
Li, Jian, Sai, Tao, Berger, Marc, Chao, Qimin, Davidson, Diane, Deshmukh, Gaurav, Drozdowski, Brian, Ebel, Wolfgang, Harley, Stephen, Henry, Marianne, Jacob, Sara, Kline, Brad, Lazo, Ella, Rotella, Frank, Routhier, Eric, Rudolph, Kathryn, Sage, Jeaneen, Simon, Paul, Yao, Jun, Zhou, Yuhong, Kavuru, Mani, Bonfield, Tracey L., Thomassen, Mary Jane, Sass, Philip M., Nicolaides, Nicholas C., Grasso, Luigi. Human antibodies for immunotherapy development generated via a human B cell hybridoma technology. Proceedings of the National Academy of Sciences. March 2006; 103(10): 3557-3562. http://hdl.handle.net/10342/3343. Accessed January 16, 2019.
East Carolina University