Therapeutic antibody, monoclonal antibodies

Hunt G. and Nashabeh W., Capillary electrophoresis sodium dodecyl sulfate nongel sieving analysis of a therapeutic recombinant monoclonal antibody a biotechnology perspective, Anal. Chem. 71, 2390,1999. 

Mammalian cells are commonly employed for the production of therapeutic and diagnostic proteins, since they are able to correctly synthetize the large and complex structures that the human body requires as medicine [1]. Nowadays, they are employed for the large-scale production of recombinant therapeutic proteins, monoclonal antibodies (MAbs) and viruses used in the preparation of vaccines (e.g. against rabies, hepathytis B, polio, etc) [2]. An overview of some licensed/approved products derived from mammalian cell culture is given in Table 1. 

Dudzinski DM (2004), Reflections on historical, scientific, and legal issues relevant to designing approval pathways for generic versions of recombinant protein-based therapeutics and monoclonal antibodies, Flarvard Law School, Thesis. Available at http //leda.law.harvard.edu/leda/data/630/(accessed February 2006). 

The set of ATs that circulate in the bloodstream require a modification to this IHC protocol. These are situations where the disease stimulates abnormal production of a hormone/growth factor by one tissue that has deleterious effects on a second organ and a therapeutic neutrahzing monoclonal antibody that ehminates the function of this ectopic factor is sought. To verify the suspected elevated circulating levels of these factors, sera from patients with the clinical condition is compared to a set of valid controls using immunochem-istry. 

Green, L. L, Antibody engineering via genetic engineering of the mouse, XenoMouse strains are a vehicle for the facile generation of therapeutic human monoclonal antibodies. J. Immunol. Methods 1999, 231(1-2), 11-23. 

Kamoda, S., Ishikawa, R., and Kakehi, K., Capillary electrophoresis with laser-induced fluorescence detection for detailed studies on N-linked oligosaccharide profile of therapeutic recombinant monoclonal antibodies, J. Chromatogr. A, 1133, 332-339, 2006. 

Monoclonal antibodies (mAh) are molecules that recognize and bind a specific foreign substance called an antigen. They are produced from a single clone of B lymphocytes. Conventionally, mouse mAh have been generated for experimental and diagnostic use. Techniques have been developed to humanize mouse mAh to facilitate their therapeutic use in humans. It is also now possible to make mAh which are fully human. 

Commercially available dtugs used for therapeutic therapy comprise up to date mainly injectable monoclonal antibodies like Infliximab (Remicade ) and Adalimumab (Humira ) or TNF-receptor derivatives like Etanercept (Enbrel ) (Fig. 3). One possible way of action of these reagents is the neutralization of TNF, thereby blocking its inflammatory effects and dampening (auto)immune responses [3, 4]. 

Adalimumab (Humira ) is a folly human anti-TNF monoclonal antibody that is mainly used in combination with methotrexate to treat rheumatoid arthritis in adults [3]. Meanwhile, it is also used against arthritis of psoriasis and ankylosing spondylitis. Its therapeutic value in Crohn s disease is under clinical trial. 

In addition to the three types of immunological product that are generally available there are two further types synthetic peptide vaccines and monoclonal antibodies. Both have been extensively investigated but neither has, as yet, a place in conventional prophylaxis or therapeutics. 

A monoclonal antibody-based ELISA has been utilized to determine ceftiofur levels in milk. The authors noted that matrix interference occurred, but a 1 100 dilution lowered the interference, and a 1 1000 dilution eliminated the matrix interference. Because of the high dilution, samples could not be measured below l.Opgkg The assay measured ceftiofur, its major metabolite desfuroylceftiofur, and ceftiofur protein conjugates and has been utilized to measure residues in milk from cows treated with therapeutic doses of the drug. The results from the incurred residue correlated well with a previous study using radiolabeled ceftiofur, confirming the detection of a metabolite that was not detected by HPLC. 

---