Human antibodies for immunotherapy development generated via a human B cell hybridoma technology
Author
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 S.; Bonfield, Tracey L.; Thomassen, Mary Jane; Sass, Philip M.; Nicolaides, Nicholas C.; Grasso, Luigi
Abstract
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
Subject
Date
2006-03-07
Citation:
APA:
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 S., & 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
MLA:
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 S., 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.
May 29, 2023.
http://hdl.handle.net/10342/3343.
Chicago:
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 S. 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
May 29, 2023).
AMA:
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 S., 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
May 29, 2023.
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Publisher
East Carolina University