Tumor necrosis factor, monoclonal antibody therapy

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. 

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. 

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. 

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. 

There are five reported orthodox anticancer immune therapies (Walters, 1993, p. 56). These include BCG, interferon, interleukin-1 or interleukin-2, tumor necrosis factor or TNF (necrosis means death), and monoclonal antibodies. The first, BCG (Bacillus Cahnette-Guerin), is described as a tuberculin vaccine that stimulates the body to kill cancer cells, and it has been said that it apparently works best when administered with chemotherapy. (However, BCG has entered into mainstream cancer therapy as a treatment against bladder cancer.) Interferon, a family of proteins, is approved for only two kinds of cancer and may prove to be of limited value in others. Both interferon and the interleukins (another family of proteins) have mainly proved to be disappointments. TNF, produced in minute quantities in the body and otherwise expensive, has achieved some dramatic results on mouse cancer. With... 

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. 

---