Monoclonal antibodies therapeutic rheumatoid arthritis

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. 

The most widely studied therapeutic proteins produced in plants include monoclonal antibodies for passive immunotherapy and antigens for use as oral vaccines [40]. Antibodies against dental caries, rheumatoid arthritis, cholera, E. coli diarrhea, malaria, certain cancers, Norwalk virus, HIV, rhinovirus, influenza, hepatitis B virus and herpes simplex virus have been produced in transgenic plants. However, the anti-Streptococcus mutans secretory antibody for the prevention of dental caries is the only plant-derived antibody currently in Phase II clinical trials [40]. Until recently, most antibodies were expressed in tobacco, potato, alfalfa, soybean, rice and wheat [9], It has been estimated that for every 170 tons of harvested tobacco, 100 tons represents harvested leaves. A single hectare could thus yield 50 kg of secretory IgA [3, 41]. Furthermore, it has been estimated that the cost of antibody production in plants is half that in transgenic animals and 20 times lower than in mammalian cell cul-... 

Maini, R. N., Breedveld, E. C., Kalden, J. R., et al. (1998) Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis and Rheumatism. 41, 1552-1563. 

Many attempts have been made to link monoclonal antibodies specific for antigenic determinants on cancer cells to protein toxins such as ricin (Box 29-A). It is hoped that this may provide an effective way of carrying toxins into cancer cells/ 1 r Therapeutic human monoclonal antibodies are already in use as antirejection drugs for kidney transplantation, for treatment of rheumatoid arthritis, Crohn disease, and for some types of cancer/... 

The first therapeutic antibody approved (Orthoclone OKT-3 or Muromonab CD3, 1986) was indicated not for cancer treatment, but for controlling acute rejection of transplanted organs (kidney, heart, and liver). Nowadays, other clinical indications such as asthma, rheumatoid arthritis, psoriasis, and Crohn s disease are treated with mAbs (see Chapter 17) (Antibody Engineering and Manufacture, 2005 Monoclonal Antibodies and Therapies, 2004 Hot Drugs, 2004 Walsh, 2004). 

Good assay reproducibility and recovery were observed for neat (undiluted) normal human serum and serum from rheumatoid arthritis patients for quantitation of a fully human anti-TNF-a monoclonal antibody [86]. It has also been reported that excess therapeutic antibodies present in serum were tolerated better in an assay for the detection of antitherapeutic antibodies based on the MSD ECL device [91]. Furthermore, the ECL procedure has been reported to be stable over a broad range of magnetic bead concentrations, probe concentrations, and hybridization conditions for a nucleic acid binding assay, making these assays more versatile and easier to transfer from one laboratory to another [88]. 

Therapeutic Agents Targeting TNF-oc. The Streptococcus pneumoniae host resistance model is also valuable for evaluating the importance of macrophage cytokines on bacterial host resistance. Human biological therapeutics targeting inhibition of TNF-a have been used to treat inflammatory autoimmune diseases such as rheumatoid arthritis. Decreased TNFa as a result of treatment with monoclonal antibodies (mAb) to TNF-a has an effect on several biomarkers of infection (Takashima et al, 1997 van der Poll et al, 1997 Benton et al., 1998 O Brien et al, 1999). These studies have reported that treatment of mice with a mAb to TNF-a results in altered levels of TNF-a in the lungs... 

Weisman M FI, Moreland L W, Furst D E, et al. (2003). Efficacy, pharmacokinetic, and safety assessment of adalimumab, a fully human anti-tumor necrosis factor-alpha monoclonal antibody, in adults with rheumatoid arthritis receiving concomitant methotrexate A pilot study. Clin. Therapeut. 25 1700-1721. 

These data demonstrate the involvement of chemokines and their receptors in inflammatory joint disease. Further information on the role of chemokines and chemokine receptors should come from the use of transgenic or knockout mice in animal models of arthritis. It is clear that blocking the interactions between chemokines and their receptors using antichemokine, antichemokine receptor monoclonal antibodies, or chemokine receptor antagonists may prove to be of therapeutic value in the control inflammatory diseases such as rheumatoid arthritis. 

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