Construction of Sea Anemone Cytolysin-based Immunotoxins for Selective Killing of Cancer Cells
Abstract
Sea anemone cytolysins based Immunotoxins (ITs) constitute an attractive alternative for construction of IT for selective killing cancer cells. In fact the pore-forming cytolysins from sea anemones, actinoporins, are one of the most potent groups of pore-forming proteins in nature. The requirement of internalization and translocation to the cytosol and the degradation of most of the IT routed to the lysosomes after internalization would be some of the critical factors determining the cytotoxicity of the classical ITs that would be overcome in such constructions. The results obtained using as toxic moiety actinoporins have supported the feasibility of directing these cytolysins to the surface of either cancer cells or even the parasite Giardia duodenalis. However the main problem of the IT constructed in such fashion is the lack of the specificity associated with the toxin moiety, a common problem of most membrane-acting ITs. An approach designed to overcome this limitation is the production of ITs using PFTs activated by tumour-associated proteases. Currently, the construction of an MMP-activated IT based on an actinoporin is in development. The alternative of using actinoporin based ITs as components of chemotherapeutic cocktails and the future prospects of employing only the N-terminal region of actinoporins for construction of IT are discussed.
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