References

Akiyama, S., Gottesman, M.M., Hanover, J.A., FitzGerard, D., Willingham, M.C., and Pastan, I. (1984) Verapamil enhances the toxicity of conjugates of epidermal growth factor with Pseudomonas exotoxin and transferrin receptor with Pseudomonas exotoxin. J. Cell. Physiol., 120, 271-79. Amlot, P.L., Stone, M.J., Cunningham, D., Fay, J., Newman, J., Collins, R., May, R., McCarthy, M., Richardson, J., Ghetie, V., et al. (1993) A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin...

Autoimmune disease

The therapeutic application of DAB389IL-2 is not limited to the treatment of T-cell derived malignant disease. DAB389IL-2 is a potential therapeutic for any disease where the underlying etiology is mediated by activated T cells, such as many autoimmune diseases. To date, the clinical studies conducted to evaluate the efficacy of Ontak for the treatment of autoimmune disease have been limited to psoriasis and rheumatoid arthritis (RA). Common examples of other T lymphocyte mediated diseases...

Treatment of autoimmune diseases with engineered toxins Fusion toxins

The interleukin-2 receptor (IL-2R) is upregulated on proliferating T lymphocytes following antigen stimulation. Activated T cells bearing the high-affinity IL-2R accumulate as cellular infiltrates in autoimmune diseases. Numerous IT constructs target the high-affinity IL-2R, which exists as a complex of the 55-kDa a-chain (p55 or CD25), the 75-kDA jS-chain (p75 or CD122) and a y-chain. While a low-affinity IL-2R (j-, y-chains) is expressed on most T cells, the high-affinity receptor (a-, j-,...

Psoriasis

Psoriasis is a common chronic inflammatory dermatosis affecting 2 of the US population. As described by Drew (2000), psoriasis is a chronic, recurrent skin disorder that can range in severity from a few mild lesions to severe exfoliation. It is sometimes associated with arthritis, myopathy, enteropathy, spondylitic heart disease, and AIDS. The most typical lesion is a well demarcated, pink to salmon colored plaque covered by loosely adherent scales that are characteristically silver-white in...

Other applications for DAB389IL2

The partial success of DAB486IL-2 and DAB389IL-2 as a therapeutic for psoriasis and rheumatoid arthritis demonstrates the potential application of IL-2 targeted diphtheria-based fusion protein constructs for the treatment of T-cell mediated autoimmune disease. Due to the selective activity of DAB389IL-2, it is a potential therapeutic only for those patients whose autoimmune disease is mediated by the activation and proliferation of T cells. In these patients, the reduced toxicity of DAB389IL-2...

Info

Allured, V.S., Collier, R.J., Carroll, S.F., and McKay, D.B. 1986 . Structure of exotoxin A of Pseudomonas aeruginosa at 3.0-Angstrom resolution. Proceedings of the National Academy of Sciences, Anasetti, C., Hansen, J.A., Waldmann, T.A., Appelbaum, F.R., Davis, J., Deeg, H.J., Doney, K., Martin, P.J., Nash, R., Storb, R., Sullivan, K.M., Witherspoon, R.P., Binger, M.-H., Chizzonite, R., Hakimi, J., Mould, D., Satoh, H., and Light, S.E. 1994 . Treatment of acute graft-versus-host disease with...