Tumor necrosis factor, monoclonal antibody

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). 

Tumor necrosis factor Monoclonal antibody preparations y-Globulin preparations Hepatitis B surface antigen... 

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. 

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. 

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. 

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. 

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. 

Chichemanian RM, Bretagne S, Emilie D, Lemann M, Lorthololary O, Mariette X. Risk of tuberculosis is higher with antitumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therap5i the three-year prospective French research axed on tolerance of biotherapies registry. Arthritis Rheum 2009 60 1884-94. 

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. 

C21. Cohen, J., and Carlet, J., INTERSEPT An international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-a in patients with sepsis. Crit. Care Med. 24, 1431-1440(1996). 

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). 

Mammalian cell suspension cultures are the preferred choice for large-scale recombinant protein production in stirred-tank bioreactors. The most widely used systems are Chinese hamster ovary (CHO) cells and the murine myeloma fines NSO and SP2/0. In half of the biological license approvals from 1996-2000, CHO cells were used for the production of monoclonal antibodies and other recombinant glycosylated proteins, including tPA (tissue plasminogen activator) and an IgGl fusion with the tumor necrosis factor (TNF) receptor, the latter marketed as Enbrel [7]. 

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). 

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. 

Mecfianism of Action A monoclonal antibody that binds specifically to tumor necrosis factor (TNF) alpha, blocking its interaction with cell surface TNF receptors, Tfier-apeutic Effect Reduces inflammation, tenderness, and swelling of joints slows or prevents progressive destruction of joints in rheumatoid arthritis. 

Tumor necrosis factor-alpha monoclonal antibody [SY]... 

Some drugs situations are frankly confusing and need to be explored in greater depth. For example, tumor necrosis factor (TNF) is produced in the body as a natural defense against the many spontaneous tumors that arise in the body and has been suggested as a treatment for cancer, which may very well be effective under some conditions. However, TNF is also believed to be involved in the pain associated with rheumatoid arthritis, and monoclonal antibodies with specific activity against TNF are now on the market. The use of TNF is therefore a complex issue and needs to be evaluated with considerable care. 

Hudziak, R. M., Lewis, G. D., Winger, M., Fendly, B. M., Shepard, H. M., and Ullrich, A., 1989. pl85 HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol. Cell Biol. 9 1165-1172. 

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. 

As of 2008, 25 therapeutic monoclonal antibodies (mAbs) mAbs had been approved for clinical use in the United States, and with over 400 antibodies being in preclinical and clinical development further increase of antibody therapies is assured (10, 11). As a general rule, the Fc fragment is a key component of therapeutic mAb design because it extends their pharmacokinetics. Inclusion of the Fc from IgG is also a key component of other bioactive proteins where prolongation of pharmacokinetics is desired, e.g., the tumor necrosis factor receptor (TNFR) fusion protein etan-ercept (Enbrel ) (12). Thus for both therapeutic antibodies and Fc-fusion proteins, the FcRn interaction is a generalized way to exploit FcRn protection to achieve the benefits of extended persistence in vivo. 

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. 

Carlet,J., Cohen,J., Andersson,J. dal. (1994). INTERSEPT an international efficacy and safety study of monoclonal antibody (Mab) to human tumor necrosis factor (hTNF) in patients with sepsis syndrome. In Program and Abstracts of the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy. Orlando, FL, Oct. 4-7,1994, Abstract 7. American Society for Microbiology, Washington D.C. 

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. 

Abramowicz D, Schandene L, Goldman M, et al. Release of tumor necrosis factor, interleukin-2, and gamma-interferon in serum after injection of OKT3 monoclonal antibody in kidney transplant recipients. Transplantation 1989 47 606. 

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