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Denileukin diftitox


ACCESSION NB: DB00004 (BIOD00084, BTD00084)


TYPE: biotech


GROUP: approved


DESCRIPTION:
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.

VOLUME OF DISTRIBUTION: 0.06 to 0.09 L/kg

CATEGORIES:
Antineoplastic Agents

ABSORPTION: Not Available

INDICATION:
For treatment of cutaneous T-cell lymphoma

PHARMACODYNAMICS:
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:
Denileukin diftitox 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.

PROTEIN BINDING:
Not Available

TOXICITY:
Not Available

AFECTED ORGANISMS:
Humans and other mammals