Clinical experience with denileukin diftitox (ONTAK).

Abstract:

:Denileukin diftitox (ONTAK; Seragen Inc, San Diego, CA) is a fusion protein designed to direct the cytocidal action of diphtheria toxin to cells that overexpress the IL-2 receptor. The human IL-2 receptor exists in three isoforms: low (CD25), intermediate (CD122/CD132), and high (CD25/CD122/CD132) affinity. The high-affinity form of this receptor is expressed on activated T lymphocytes, activated B lymphocytes, and activated macrophages. A number of leukemias and lymphomas, including cutaneous T-cell lymphoma, chronic lymphocytic leukemia, and B-cell non-Hodgkin's lymphoma, express a component of the receptor. Ex vivo studies have shown that denileukin diftitox interacts with the high- and intermediate-affinity IL-2 receptor on the cell surface and undergoes internalization. Subsequent cleavage in the endosome releases the diphtheria toxin into the cytosol, which then inhibits cellular protein synthesis, resulting in rapid cell death. This article examines the clinical profile and potential benefits of denileukin diftitox in the treatment of cutaneous T-cell lymphoma and other hematologic disorders.

journal_name

Semin Oncol

journal_title

Seminars in oncology

authors

Foss F

doi

10.1053/j.seminoncol.2005.12.017

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

S11-6

issue

1 Suppl 3

eissn

0093-7754

issn

1532-8708

pii

S0093-7754(05)00511-7

journal_volume

33

pub_type

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