Production of a monoclonal antibody by ascites, hollow fiber system, and transgenic plants for vaccine production using CB.Hep-1 mAb as a study case

Biotechnology and Bioprocess Engineering 17: 145-159 (2012) DOI 10.1007/s12257-011-0196-2

RESEARCH PAPER

Production of a Monoclonal Antibody by Ascites, Hollow Fiber System, and Transgenic Plants for Vaccine Production Using CB.Hep-1 mAb as a Study Case

Rodolfo Valds, Andrs Tamayo, Marcos Gonzlez, Sigifredo Padilla, Dborah Geada, William Ferro, Lorely Mil, Leonardo Gmez, Rosario Alemn, Alberto Leyva, Cristina Garca, Otto Mendoza, Tatiana Alvarez, Lamay Dorta, Yanet Villega, Dobin Cecilia, Hasel Aragn, Tatiana Gonzlez, Mayln La O, and Jorge Lpez

Received: 28 April 2011 / Accepted: 2 September 2011 The Korean Society for Biotechnology and Bioengineering and Springer 2012

1. Introduction

Antibodies are biological molecules with a wide range of applications, including medical diagnosis and therapy, immunomodulation of physiological processes, release of vaccine lots, and industrial purification [1]. In an August 1975 letter to Nature, Milstein and Khler described how they generated monoclonal antibodies (mAbs) from a mixture of many different antibodies and produced an immune response. They fused B cells from a mouse immunized with a particular antigen to mouse bone-marrow-cancer cells (myelomas) to generate hybridoma cells. B cells conferred antibody production capability, whereas the myeloma cells enabled hybridomas to divide indefinitely. These researchers were awarded the Nobel Prize for Physiology and Medicine for their contribution [2]. Since then, large-scale mAb production methods have been developed [3,4], but their development has been governed by cost, ethic, and bio-safety issues, as well as by the rapid saturation of worldwide facilities for classical mammalian cell culture.

Hybridoma cell lines are traditionally grown as ascites tumors to produce large quantities of mAbs. In general, this procedure produces antibody titers approximately 1,000 ~ 10,000-fold higher than those obtained by tissue culture. Thus, the main advantage of ascites is the extremely high antibody yield. However, this advantage and its applicability to almost any kind of hybridoma cell line is outweighed by a number of disadvantages [5].

Several in vitro alternatives are available, including standard static or agitated suspension cell cultures, membrane- and matrix-based culture systems, and high cell-

Abstract Monoclonal antibody (mAb) production methods (ascites, in vitro technologies, transgenic animals, and dicot or monocot transgenic plants; moss, algae) have been improved since they were first developed in 1975. In this study, we illustrate a summary of a study case in which mice, a...