The emerging role of ricin A-chain immunotoxins in leukemia and lymphoma

Since MRD is the major cause for relapses of malignant diseases, strategies utilizing ITs to target tumor cells surviving conventional treatment have attracted scientific and clinical interest. Many different ITs against various blood-borne as well as solid malignancies have demonstrated specific potent anti-tumor effects in vitro and in animal models. Some of these have already undergone clinical phase I/II trials. The dose-limiting toxicities of RTA ITs include manifestation of VLS presenting as decreased urinary sodium excretion, hypoalbuminemia, fatigue, hypotonia, myalgia, pulmonary edema, or rhabdomyolysis. Problems encountered clinically include the development of HAMA, HARA, and HACA and the selection of antigen- deficient malignant clones. Most clinical trials performed with ITs so far were conducted in heavily pretreated patients presenting with high tumor burdens. Thus, the responses observed with ITs in these trials are very encouraging and warrant further exploration.