Ontak

Ontak is the brand name of denileukin diftitox, a recombinant fusion protein that combines interleukin-2 with a truncated form of diphtheria toxin. It is designed to selectively target cells that express the IL-2 receptor (CD25), including many malignant T cells in certain lymphomas.

Mechanism: Ontak binds to the IL-2 receptor on the cell surface, is internalized, and releases the diphtheria toxin fragment into the cytosol. The toxin inhibits protein synthesis by inactivating elongation factor-2, causing cell death. The selectivity for CD25-expressing cells aims to spare nonexpressing cells but may affect activated normal T cells, NK cells, and other cells expressing CD25.

Indication and usage: Ontak has been used primarily for adults with CD25-expressing cutaneous T-cell lymphoma (CTCL), such as mycosis fungoides with persistent or progressive disease, after failure of at least one systemic therapy. It is given by intravenous infusion, with treatment cycles spaced several weeks apart, typically administered for a limited number of cycles depending on response and tolerability.

Clinical considerations: Efficacy is modest, with response rates in a subset of patients and duration of response variable. Adverse events include flu-like symptoms, infusion reactions, dehydration, electrolyte disturbances, and serious toxicities such as capillary leak syndrome, edema, pulmonary toxicity, hepatotoxicity, and increased risk of infections. Careful monitoring during infusions is required.

Regulatory status: Ontak was approved in 1999 for CTCL but faced safety concerns and supply issues, leading to its limited availability and discontinuation of production in many markets. As a result, it is not widely used in current practice, with newer therapies for CTCL available.