Anti-tumor necrosis factor antibody

In E. Coli bacterial lysates, the proteome (i.e., the full array of proteins produced) was analyzed by isoelectric focusing and mass spectrometry.97 A comparison of capillary electrophoretic separation and slab gel separation of a recombinant monoclonal antibody demonstrated that the precision, robustness, speed, and ease-of-use of CE were superior.98 Seventy-five proteins from the yeast ribosome were analyzed and identified by capillary electrophoresis coupled with MS/MS tandem mass spectrometry.99 Heavy-chain C-terminal variants of the anti-tumor necrosis factor antibody DE7 have been separated on capillary isoelectric focusing.100 Isoforms differing by about 0.1 pi units represented antibodies with 0,1 or 2 C-terminal lysines. 

P17. van der Poll, T., Levi, M Van Deventer, S. J., Ten Cate, H., Haagmans, B. L., Biemond, B. J., Buller, H. R Hack, C. E., and Ten Cate, J. W., Differential effects of anti-tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 83,446-451 (1994). 

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. 

Keystone, E. C., Kavanaugh, A. E., Sharp, J. T., et al. (2004) Radiographic, cUnical, and functional outcomes of treatment with adaUmumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy a randomized, placebo-controUed, 52-week trial. Arthritis and Rheumatism. 50, 1400-1411. 

The present primary mode of therapy for these diseases involves the use 5-amino-salicylate (5-ASA) products. Often patients require additional medications, including corticosteroids, to help induce remission and various immune modulators, such as azathioprine, 6-mercaptopurine or methotrexate, to maintain remission. In Crohn s disease certain antibiotics, such as metronidazole and ciprofloxacin, and infliximab Remi-cade), an anti-tumor necrosis factor-a(TNFa) antibody, also have been used. The pharmacology of antibiotics, immunosuppressive drugs, and corticosteroids is discussed in Chapters 43,57, and 60, respectively. 

Taylor MJ, Lucier GW, Maliler JF, et al. 1992. Inhibition of acute TCDD toxicity by treatment with anti-tumor necrosis factor antibody or dexamethasone. Toxicol Appl Pharmacol 117 126-132. 

Maini, R., St. Clair, E. W., Breedveld, F., Furst, D., Kalden, J., Weisman, M., Smolen, J., Emery, P. 1999. Infliximab (chimeric anti-tumor necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate a randomised phase HI trial. Attract study group. Lancet 354 1932-1939. 

Fisher, C. J., Opal, S. M., Dhainaut, J. F., Stephens, S., Zimmermann, J. L., Nightingale, P. et al. (1993). Influence of an anti-tumor necrosis factor monoclonal antibody on cytokine levels in patients with sepsis. Cril. Care. Med. 21, 318-327. 

Reinhart, K., Wiegand-Lohnert, C., Grimminger, F., Kaul, M., Withington, S., Treacher, D., Eckart, J. et al. (1996). Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock A multicenter, randomized, placebo-controlled, doseranging study. Crit. Care Med. 24, 733-742. 

Boekstegers, P., Weidenhofer, S., Zell, R, et al. (1994). Repeated administration of a F(ab )2 fragment of an anti-tumor necrosis factor a monoclonal antibody in patients with severe sepsis Effects on the cardiovascular system and cytokine levels. Shock la, 1237-1245. 

Paleolog, E. W., Hunt, M., Elliott, M., Feldmann, M., Maini, R. N., and Woody, J. (1996). Deactivation of vascular endothelium by monoclonal anti tumor necrosis factor a antibody in rheumatoid arthritis. Arthritis Rheum. 39, 1082-1091. 

Tak, P. P., Taylor, P. C., Breedveld, F. C., Smeets, T.J., Daha, M. R., Kluin, P. M. etal. (1996). Decrease in cellularity and expression of adhesion molecules by anti-tumor necrosis factor a monoclonal antibody treatment in patients with rheumatoid arthritis. Arthritis Rheum. 39, 1077-1081. 

D haens, G., van Deventer, S., van Hogezand, R., Chalmers, D., Kothe, C., Baert, F., Braakman, T., Schaible, T., Geboes, K., and Rutgeerts, P. (1999). Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn s disease A European multicenter trial. Gastroenterology 116, 1029-1034. 

Chatenoud L. OKT3-induced cytokine-release syndrome prevention effect of anti-tumor necrosis factor monoclonal antibody. Transplant Proc 1993 25(2 Suppl 1) 47-51. 

Rutgeerts P, D Haens G, Targan S, et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn s disease. Gastroenterology 1999 17 761-769. 

Chung ES, Packer M, Lo KH, et al. Randomized, double-bUnd, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure Results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 2003 107 3133-3140. 

Weinblatt ME, Keystone EC, Furst DE, et al. AdaUmumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for flie treatment of rheumatoid arfluitis in patients taking concomitant mefliotrexate The ARMADA trial [erratum appears in Arfluitis Rheum 2003 48 855]. Arthritis Rheum 2003 48 35 5. 

Ferran C, Dy M, Sheehan K, Schreiber R, Grau G, Bluestone J, Bach JF, Chatenoud L. Cascade modulation by anti-tumor necrosis factor monoclonal antibody of interferon-y, interleukin 3 and interleukin 6 release after triggering of the CD3/T cell receptor activation pathway. Eur J Immunol 1991 21(10) 2349-2353. 

Tilg, H., Jalan, R., Kaser, A., Davies, N. A., Offner, F. A., Hodges, S. J., Ludwiczek, O., Shawcross, D., Zoller, H., Alisa, A., Mookerjee, R. P., Graziadei, L, Datz, C., Trauner, M., Schuppan, D., Obrist, P., Vogel, W. and Williams, R. Anti-tumor necrosis factor-alpha monoclonal antibody therapy in severe alcoholic hepatitis. J Hepatol 38 (2003) 419 25. 

Prosthetics CytoTAb target anti-tumor necrosis factor alpha polyclonal antibody (licensed in late 2005 to Astra Zeneca)... 

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. 

Fig. 36.30. Anti-tumor necrosis factor (TNF) agents. Etanercept is the extracellular portion of the human TNFR fused to the Fc domain of human immunoglobulin Ig G1. Infliximab is a partially humanized monoclonal antibody against TNFa. The Fv domains are derived from mouse antihuman sequences, whereas the Fc domain is composed of human lgG1 sequences. Adalimumab is fully humanized antibody to human TNFa (Fv and Fc derived from human sequences). Rituxan is a partially humanized monoclonal antibody against CD40. The Fv domains are derived from mouse antihuman sequences, and the Fc domain is composed of human lgG1 sequences.

Following treatment of patients with rheumatoid arthritis with low and high dose anti tumor necrosis factor-a (TNF) or placebo, serum MMP-1 and MMP-3 levels were assessed by Brennan et al. (BIO). In both antibody-treated groups, a significant decrease in serum MMP-3 levels at all time points was observed, reduced maximally to 41% of pre-infusion values at day 7. MMP-1 levels were also reduced, but less dramatically than with MMP-3. While serum MMP-3 levels correlated with C-reactive protein both prior to and following therapy, Brennan et al. concluded that it remains to be demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and bone resorptive processes which are evident in this disease. Catrina et al. (C2) also examined the effect of anti-tumor necrosis factor-a therapy (etanercept) on MMPs. Etanercept therapy downregulated serum... 

Farkas K, Nagy F, Kovacs L, V Sttmann T, Molnan T. Anti-tumor necrosis factor-a induced systemic lupus erythematosus in a patient with metastatic Crohn s disease - what is the role of anti-TNF antibody J Crohns Colitis 2013 7(4) el43-5. 

Starnes, H. F Pearee, M. K., Tewari, A., Yim, H. H., Zou, J. C., and Ambrams, J. S., Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-a challenge in mice. J. Immunol. 145,4185-4191 (1990). 

Wattiez R et al. Human bronchoalveolar lavage fluid protein two-dimensional database study of interstitial lung diseases. Electrophoresis 2000 21 2703-2712. Yanagida M et al. Matrix assisted laser desorption/ionization-time of flight-mass spectrometry analysis of proteins detected by anti-phosphotyrosine antibody on two-dimensional-gels of fibrolast cell lysates after tumor necrosis factor-alpha stimulation. Electrophoresis 2000 21 1890-1898. 

The major types of drug therapy used in IBD include aminosalicylates, glucocorticoids, immunosuppressive agents (azathioprine, mercaptopu-rine, cyclosporine, and methotrexate), antimicrobials (metronidazole and ciprofloxacin), and agents to inhibit tumor necrosis factor-a (TNF-a) (anti-TNF-a antibodies). 

Tumor Necrosis Factor There are two types of tumor necrosis factor TNF-a and TNF- 8. Of the two, TNF-a has been studied in more detail. TNF-a is a 157 amino acid polypeptide. It is a mediator of immune regulation, including the activation of macrophages and induction of the proliferation of T cells. Another TNF-a function is its cytotoxic effects on a number of tumor cells. Recent research, however, concentrates on its property in the stimulation of inflammation, particularly in the case of rheumatoid arthritis. Clinical trials are being conducted with drugs to block TNF-a with anti-TNF-a monoclonal antibodies. These antibodies target the excessive levels of TNF-a in the synovial fluid of joints and provide relief to sufferers of rheumatoid arthritis (Exhibit 4.10). 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Anti-TNF antibodies, eg, infliximab, others Bind tumor necrosis factor and prevent it from binding to its receptors Suppression of several aspects of immune function, especially ThI lymphocytes Infliximab Moderately severe to severe Crohn s disease and ulcerative colitis others approved in Crohn s disease Infusion reactions reactivation of latent tuberculosis increased risk of dangerous systemic fungal and bacterial infections... 

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