Therapeutic Challenges

The majority of literature evaluating immunotoxins consists of data from phase I trials. While these studies have collectively shown that therapeutic serum levels of toxin can be achieved with acceptable toxicity, much research remains to be done. The compounds have been plagued with high toxicity profiles and low response rates.30 Many different MoAb-toxin combinations have been studied and the adverse effect profile has remained surprisingly consistent. Most of the phase I dose-escalation trials have been limited by the development of a vascular leak syndrome; peripheral edema, pulmonary edema, weight gain, hypoalbu-minemia, hypotension, and pericardial effusions are thought to be due to toxin-mediated endothelial dam-age.530 Hypersensitivity reactions are common as well, along with fever, malaise, and nausea. Further complicating these hypersensitivity responses is the fact that patients can react to one or both components of the

Immunotoxins currently under investigation for hematologic malignancies31,32

Compound

Target

Toxin

Clinical use

DAB389-IL2 (Ontak)

Interleukin 2 receptor

Diptheria toxin

Cutaneous T-cell lymphoma

Anti-TAC (Fv)-PE38 (LMB-2)

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