Monoclonal antibody, production

Most work on chemical stress was done with hybridoma cells since they are widely used for industrial relevant monoclonal antibody production but... 

Determination of Monoclonal Antibody Productivity in a Dialyzed Chemostat... 

The objective of this exercise is to use the techniques developed in Section 7.3 of this book to determine the specific monoclonal antibody production rate (qiw) during the batch start-up and the subsequent continuous operation. 

At time t=212 h the continuous feeding was initiated at 5 L/d corresponding to a dilution rate of 0.45 d . Soon after continuous feeding started, a sharp increase in the viability was observed as a result of physically removing dead cells that had accumulated in the bioreactor. The viable cell density also increased as a result of the initiation of direct feeding. At time t 550 h a steady state appeared to have been reached as judged by the stability of the viable cell density and viability for a period of at least 4 days. Linardos et al. (1992) used the steady state measurements to analyze the dialyzed chemostat. Our objective here is to use the techniques developed in Chapter 7 to determine the specific monoclonal antibody production rate in the period 212 to 570 h where an oscillatory behavior of the MAb titer is observed and examine whether it differs from the value computed during the start-up phase. 

Linardos, T., "Kinetics of Monoclonal Antibody Production in Chemostat Hybrid-oma Cultures", Ph D. thesis, Dept, of Chemical Petroleum Engineering, University of Calgary, AB, Canada, 1991. 

Linardos, T.I., N. Kalogerakis, L.A. Behie and L.R. Lamontagne, "Monoclonal Antibody Production in Dialyzed Continuous Suspension Culture", Biotechnol. Bioeng, 39, 504-510 (1992). 

Monoclonal antibody production In vitro production of monoclonal antibodies EU... 

A. Gebbert, M. Alvarez-Icaza, H. Peters, V. Jager, U. Bilitewski, and R.D. Schmid, On-line monitoring of monoclonal antibody production with regenerable flow-injection immuno systems. J. Biotechnol. 32, 213-220 (1994). 

Generation of antibodies that can recognize and bind to specific viruses is straightforward. A sample of live or attenuated virus, or a purified component of the viral caspid, can be injected into animals to stimulate polyclonal antibody production (or to facilitate monoclonal antibody production by hybridoma technology). Harvested antibodies are then employed to develop specific immunoassays that can be used to screen test samples routinely for the presence of that specific virus. Immunoassays capable of detecting a wide range of viruses are available commercially. The sensitivity, ease, speed and relative inexpensiveness of these assays render them particularly attractive. 

The basis of monoclonal antibody production by hybridoma technology... 

Dinnis, D. and James, D. 2005. Engineering mammalian cell factories for improved recombinant monoclonal antibody production lessons from nature Biotechnology and Bioengineering 91(2), 180-189. 

Advanced biotechnology and monoclonal antibody production have provided... 

The S6 document also mentions monoclonal antibody products. Indeed, many of the considerations for rDNA products are also applicable to monoclonal antibodies (including hybridized antibodies). With monoclonal antibodies, there is the additional concern of crossreactivity with nontarget molecules. 

Anon. (1997h). Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use. http //www.fda.gov/cber/cberftp.html... 

Fig. 1.4 Monoclonal antibody production. Adapted from http //www.accessexcellence.org/RC/ VL/GG/monoclonal.html...

Lubiniecki AS. Monoclonal antibody products achievement and prospects. Bioprocessing Journal 2(Mar/Apr) 21-26 (2003). 

A further advance in antibody technology is the development of transgenic mouse human strains. XenoMouse animals have been engineered in such a way that they now produce exclusively human antibodies rather than murine antibodies when immunized. The use of XenoMouse animals to produce MAbs avoids the need for any engineering of the antibody genes, since the products are already 100% human protein. XenoMouse animals are fully compatible with standard hybridoma technology and can be readily adopted by laboratories experienced in monoclonal antibody production [56]. 

Ascites production, however, suffers from a number of drawbacks. It is costly, and the product is contaminated by significant levels of various mouse proteins, rendering subsequent downstream processing more complex. As a result, monoclonal antibody production by standard animal cell culture techniques has become the method of choice for the production of pharmaceutical-grade monoclonal antibody preparations. 

In this section we will focus primarily on recombinant proteins. We will discuss strategies specific to monoclonal antibody production in the introduction to antibodies and derivatives (Chapter 10). Issues specific to peptides will be discussed in the... 

Figure 10.3. Schematic representation of monoclonal antibody production using immortalized hybrid cells that secrete antibodies selective for the target antigen. The mortal, immune B cells Isolated from mice immunized with a target antigen are fused with myeloma, immortal B cells that express defective antibodies. The selecting of antigen-specific, immortal hybrid cells (hybridomas) results in identification of unique clones of cells that express antibodies with high specificity and affinity (monoclonal antibodies). These cells are cloned and expanded for large-scale monoclonal antibody preparations.

Deo YM, Mahadevan MD, Fuchs R. Practical considerations in operation and scale-up of spin-filter based bioreactors for monoclonal antibody production. Biotechnol Prog 1996 12 57-64. 

FDA Guidance for Industry on the Submission of Chemistry, Manufacturing, and Controls Information for a Therapeutic Recombinant DNA-Derived Product or a Monoclonal Antibody Product for In Vivo Use (August 1996)... 

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