Chimeric proteins A novel approach for eliminating specific cell populations for targeted human therapy

Ahmi Ben-Yehudah, Ruth Belostotsky, Rami Aqeilan, Yehudith Azar, Ida Steinberger-Levy, Ala Fishman, Amotz Nechushtan, Shai Yarkoni, Haya Lorberboum-Galski

Research output: Chapter in Book/Report/Conference proceedingChapter


In the last few years a new approach for targeted therapy of human diseases was developed using cytotoxic molecules that were produced by gene fusion techniques. This class of molecules termed chimeric proteins comprises both the cell targeting and the cell killing moieties. As killing moieties, portions of toxins such as pseudomonas exotoxin (PE) or diphtheria toxin (DT) are used. Through ADP-ribosylation, PE and DT act by inactivating elongation factor 2. This causes the irreversible arrest of protein synthesis in eukaryotic cells leading to cell death (Middlebrook and Dorland, 1984). Specificity is then added to the truncated or modified toxins by fusing them with recognition elements that direct the chimeric protein to selected target cells overexpressing a specific receptor/surface marker. Effective chimeric proteins have been constructed by fusing cDNA’s encoding a variety of cytokines, growth factors, single chain antibodies and many other ligands with PE, DT and additional bacterial/plant toxins (Frankel et al., 2000). The specific binding of the targeting moiety of the chimeric protein to a surface receptor/marker expressed by the targeted cells enables the elimination of the particular cell population, sparing other cell types.
Original languageAmerican English
Title of host publicationChimeric Toxins
Subtitle of host publicationCellular and molecular mechanisms of toxin action
EditorsHaya Lorberboum-Galski, Philip Lazarovici
Place of PublicationNew York
PublisherTaylor & Francis
Number of pages20
ISBN (Electronic)9780429218552
StatePublished - 1 Jan 2002


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