Recombinant immunotoxins for the treatment of Hodgkin's disease (Review)

In recent years, substantial experience has been accumulated with tumor-spe cific immunotherapeutics which seem to be effective against minimal residua l disease. The coupling of toxins to monoclonal antibodies has indicated pr omising results in early clinical trials. Recombinant DNA technology makes it possible to genetically fuse coding regions of V genes or cytokines to m odified toxin domains. These recombinant immunotoxins can easily be manipul ated to increase the cytotoxic potency or affinity. Binding single chain va riable fragments (scFv) expressed as chimeric fusion proteins on the surfac e of filamentous bacteriophages were selected on Hodgkin-derived cell lines . This technique was also used to create a new humanized anti-CD30 scFv whi ch exhibits similar binding to the CD30 antigen when compared to its murine predecessor. ScFvs were then inserted into a new bacterial expression vect or and thus fused to a deletion mutant of Pseudomonas exotoxin. Anti-CD25(s cFv)-ETA' and anti-CD30(scFv)-ETA' were isolated from E. coli periplasm and purified by metal chelate affinity and size exclusion chromatography. All immunotoxins produced showed specific cytotoxicity against Hodgkin lymphoma cell lines as documented by competitive assays. In addition, these constru cts were highly efficient in the treatment of disseminated human Hodgkin's disease in SCID mice. These in vivo data indicate a possible clinical impac t for patients with relapsed CD25- and/or CD30-positive lymphoma.