Brands, Medical Use, Clinical Data
Brands / Synonyms
Diphtheria toxin precursor; DT; NAD(+--diphthamide ADP- ribosyltransferase); Ontak; Ontak (Seragen Inc)
A recombinant DNA-derived cytotoxic protein composed of the amino acid sequences for diphtheria toxin fragments A and B (Met 1 -Thr 387 )-His followed by the sequences for interleukin-2 (IL-2; Ala 1 -Thr 133 ). It is produced in an E. coli expression system.
For treatment of cutaneous T-cell lymphoma
Denileukin diftitox (Ontak) directs the cytocidal action of diphtheria toxin to cells which express the IL-2 receptor. The human IL-2 receptor exists in three forms, low (CD25), intermediate (CD122/CD132) and high (CD25/CD122/CD132) affinity. Malignant cells expressing one or more of the subunits of the IL-2 receptor are found in certain leukemias and lymphomas including cutaneous T-cell lymphoma (CTCL). Ontak interacts with the high affinity IL-2 receptor on the cell surface and inhibits cellular protein synthesis, resulting in cell death within hours.
Mechanism of Action
Ontak binds to the high-affinity IL-2 receptor complex. The IL-2 receptor (Tac) subunit is expressed on activated but not resting lymphocytes. The diphtheria toxin associated with Ontak then selectively kills the IL-2 bearing cells.
Biotrnasformation / Drug Metabolism