denileukin diftitox

BeschreibungDenileukin diftitox was first launched as Ontak in the US for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL) whose malignant cells express the CD25 component of the IL-2 receptor. Denileukin diftitox is a diphtheria toxin fragment A - fragment B genetically fused to a human interleukin-2 (IL-2) fragment. In vivo the IL-2 fragment seeks out activated T-cells through their IL-2 receptor. After binding, the fusion protein enters the cell by endocytosis and the toxin kills the cell by inhibiting protein synthesis. Affinity, potency and half-life of this product were greatly improved by deletion of 97 amino acids on the C-terminus of the diphtheria toxin. It is, to date, one of the most extensively evaluated fusion proteins that combine a toxin with a targeting molecule. The fusion protein is expressed in Eschefichia coli strain and purified by a series of diafiltration steps and finally by reverse phase chromatography. Antibodies against Ontak were present in 92% of patients after two courses but there was no relationship between the presence of antibodies and the likelihood of responding to the drug. In a randomized, double blind, phase III trial in 71 patients with recurrent CTCL, injection for 5 days every three weeks over 8 courses produced >50% reduction in tumor burden lasting up to 4 months in 30% of patients. Other potential indications for Denileukin diftitox are for treatment of psoriasis, HIV infection, atopic dermatitis, alopecia aerata, multiple sclerosis and inflammatory bowel disease.