Abstract
Few immunotoxins or targeted toxins have become mainline cancer therapies. Still immunotoxins continue to be of major interest and subject of research and development as alternative therapies for drug resistant cancer. A major matter of concern continues to be immunogenicity exemplified by the anti-toxin response of the treated patient. Since some of our most effective toxins are bacterial in nature and bacterial proteins are highly immunogenic, this review describes some efforts to address this pressing issue.
Highlights
Over the years, numerous toxins have been utilized as targeted toxins mainly linked to antibody or antibody fragments
Diphtheria toxin (DT) serves as the catalytic portion of the drug Denileukin diftitox (Ontak), the first targeted toxin approved by the FDA for the treatment of cutaneous T-cell lymphoma in 1999
Pseudomonas exotoxin (PE) serves as the catalytic portion of the drug Moxetumomab Pasudotox (Moxe), that was approved in September 2018 by the FDA for the treatment of hairy cell leukemia (HCL)
Summary
Numerous toxins have been utilized as targeted toxins mainly linked to antibody or antibody fragments. Moxe is a chimeric molecule consisting of a single chain Fv (scFV) antibody fragment recognizing the B-cell marker CD22 spliced to truncated pseudomonas exotoxin as a single chain. These two drugs are among the very few FDA targeted toxins approved for therapy. Once internalized into the target cell, both of these protein toxins catalyze ADP-ribosylation of a single amino acid on elongation factor 2 (a key protein involved in protein translation) This halts protein synthesis and triggers a series of cellular events that culminates in apoptosis of the intoxicated cell. In the case of PE, it has been calculated that fewer than 1000 molecules of immunotoxin/cell is sufficient to cause complete tumor regressions [4]
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