The Single-Chain Immunotoxins BR96 sFv-PE40 and BR96 sFv-PE38: Potent Anti-Tumor Agents for the Treatment of Human Cancer

Published on Jan 1, 1993
· DOI :10.1007/978-1-4615-2846-3_39
Paula N. Friedman2
Estimated H-index: 2
(BMS: Bristol-Myers Squibb),
Dana Chace5
Estimated H-index: 5
(BMS: Bristol-Myers Squibb)
+ 1 AuthorsClay B. Siegall16
Estimated H-index: 16
(BMS: Bristol-Myers Squibb)
Immunotoxins are potent agents designed to be selectively cytotoxic against specific populations of cells 1,2. Such molecules are composed of a binding portion, which is specific for a cell surface antigen or receptor, linked to a cytotoxic agent, such as a protein toxin. Pseudomonas exotoxin (PE) is a protein toxin produced by the bacteria Pseudomonas aeruginosa and kills cells by ADP-ribosylating elongation factor 2, thereby halting protein synthesis 3. Analysis of the structure of PE revealed there are 3 domains of the protein involved in: 1) binding, 2) processing and translocation, and 3) ADPribosylation 4. Forms of PE that lack domain I, the binding domain, are often used in the construction of immunotoxins, as they lack the ability to bind non-specifically to the cell surface receptor.
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