The emerging role of immunotoxins in leukemia and lymphoma

Despite important advances in conventional cancer therapy, there is still a strong need for new approaches in order to reduce cancer death rates, which have not been drastically influenced in the past ten years. Since minimal residual disease is regarded as the major cause for relapses of malignant diseases, immunotherapeutic strategies utilizing monoclonal antibodies (MoAbs) or their conjugates to target 'dormant' tumor cells have increasingly attracted scientific interest. Immunotoxins (ITs) constructed by chemically linking plant or bacterial toxins to a MoAb can selectively kill their target cells when internalized after binding to specific cell surface receptors. Many different ITs against various blood-borne as well as solid malignancies have been successfully tested in vitro and in animal models. Chemically linked ITs and recombinant fusion toxins generated by using DNA technologies are currently being evaluated for their anti-tumor activity in several clinical phase I/II/III trials. While serious side effects are rare, there are 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 with massive tumor burden are admitted to early clinical studies, so that even minor responses after IT treatment are encouraging. However, minimal residual disease is expected to be most amenable to IT therapy.