Toxin-Labeled Monoclonal Antibodies

Author: Kreitman R.J.

Source: Current Pharmaceutical Biotechnology, Volume 2, Number 4, December 2001 , pp. 313-325(14)

Publisher: Bentham Science Publishers

Abstract:

To arm monoclonal antibodies (MAbs) with the power to kill malignant cells, they have been connected to toxins to create chimeric proteins called immunotoxins. Conventional immunotoxins contain a MAb chemically conjugated to a toxin which is mutated or chemically modified to minimize binding to normal cells. Examples include anti-B4-blocked ricin, targeting CD5, and RFB4-deglycosylated ricin A chain, targeting CD22. Conventional immunotoxins are capable of inducing responses in patients with hematologic malignancies, with dose-limiting toxicities being vascular leak syndrome, thrombocytopenia, and hepatic damage. Newer immunotoxins contain a recombinant ligand, either the variable domains (Fv) of a MAb, or a growth factor, fused to a truncated bacterial toxin. Bacterial toxins commonly used for this purpose include diphtheria toxin and Pseudomonas exotoxin. DAB389IL2 (Ontak) is a recently approved growth factor fusion toxin containing human interleukin-2 and diphtheria toxin and is effective in chemotherapy-resistant cutaneous T-cell lymphoma. Anti-Tac(Fv)-PE38 (LMB-2) and RFB4(dsFv)-PE38 (BL22) are two recombinant immunotoxins, targeting CD25 and CD22, respectively, in which Fvs of MAbs targeting these antigens are fused to truncated Pseudomonas exotoxin. Both LMB-2 and BL22 have exhibited clinical activity in patients with hematologic malignancies, with less vascular leak syndrome and probably less immunogenicity than the larger conventional immunotoxin conjugates. New recombinant immunotoxins are currently being engineered and developed to target other hematologic and solid tumor antigens.

Keywords: Toxin-Labeled; Monoclonal Antibodies; T-cell lymphoma; Recombinant Immunotoxin Targeting CD25; Nonspecific Toxicity; Diphtheria toxin; Vascular leak syndrome

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389201013378635

Publication date: 2001-12-01

• Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.

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