THE EMERGING ROLE OF IMMUNOTOXINS IN LEUKEMIA AND LYMPHOMA

Despite important advances in conventional cancer therapy, there is st ill a strong need for new approaches in order to reduce cancer death r ates, which have not been drastically influenced in the past ten years . Since minimal residual disease is regarded as the major cause for re lapses of malignant diseases, immunotherapeutic strategies utilizing m onoclonal antibodies (MoAbs) or their conjugates to target 'dormant' t umor cells have increasingly attracted scientific interest. Immunotoxi ns (ITs) constructed by chemically linking plant or bacterial toxins t o a MoAb can selectively kill their target cells when internalized aft er binding to specific cell surface receptors. Many different ITs agai nst various blood-borne as well as solid malignancies have been succes sfully tested in vitro and in animal models. Chemically linked ITs and recombinant fusion toxins generated by using DNA technologies are cur rently being evaluated for their anti-tumor activity in several clinic al phase I/II/III trials. While serious side effects are rare, there a re still many problems to be solved, such as the immunogenicity of the toxin and/or antibody moiety or the poor capacity of ITs to penetrate large solid tumors. At the moment only heavily pretreated patients wi th massive tumor burden are admitted to early clinical studies, so tha t even minor responses after IT treatment are encouraging. However, mi nimal residual disease is expected to be most amenable to IT therapy.