Recombinant immunotoxins for cancer therapy

Recombinant immunotoxins consist of Fv regions of tumour-selective antibodi es fused to toxins found in bacteria, plants or fungi. These toxins must be modified to remove normal-tissue binding sites but to retain all other fun ctions of cytotoxicity. The recombinant antibody fragments target the modif ied toxin to cancer cells which are killed, either by direct inhibition of protein synthesis, or by concomitant induction of apoptosis. Cells that are not recognised by the antibody fragment because they do not carry the tumo ur antigen, are spared. Many factors influence the in vivo antitumour activ ity of recombinant immunotoxins. Among them are considerations of which typ es of cancer may be the best targets for immunotoxin therapy as well as tum our specificity of the antigen that is targeted by the recombinant antibody . Other relevant issues are the affinity of immunotoxins and their ability to enter and penetrate into tissues and tumours, which in turn is dependent on the size of the protein. A great deal of protein-engineering is require d to stabilise the recombinant antibody moiety of immunotoxins, since stabi lity of the molecules is crucial for good clinical efficacy. Excellent acti vity and specificity can be observed for many recombinant immunotoxins in i n vitro assays using cultured cancer cells as well as in animal tumour mode ls. Ongoing clinical trials provide examples where the promising preclinica l data correlate with successful results in experimental cancer therapy.