NEW ORLEANS--Diphtheria toxin-based "fusion toxins" can produce durable remissions in malignancies that express the targeted receptor, and they are safe and well-tolerated, said John R. Murphy, PhD, chief of biomolecular medicine, Boston University Medical Center Hospital.
"For the first time we have been able to genetically redesign a potent biological poison and direct it toward a cell receptor of our choosing that is present on malignant cells. We are gratified that it worked and that the adverse profile is mild," Dr. Murphy said at the American Cancer Society Science Writers Seminar.
By using recombinant technology to redesign native diphtheria toxin, Dr. Murphy and his colleagues at Boston University, where he is professor of medicine, have been able to selectively intoxicate target malignant cells.
The researchers have genetically replaced the native diphtheria toxin receptor binding domain with a variety of cytokines and growth factors, including interleukin 2 (IL-2), IL-4, IL-6, epidermal growth factor (EGF), CD4, and alpha-melanocyte stimulating hormone.
The resulting "fusion toxins" are specific and highly potent in eliminating only those cells that carry the receptor recognized by the cytokine/growth factor portion of the fusion toxin. For example, the fusion toxin DAB-389 IL-2 binds, through its IL-2 receptor binding domain, to cells having the IL-2 receptor, delivering a cytotoxic component into the cell.
High-Affinity IL-2 Receptors
Cutaneous T-cell lymphoma and non-Hodgkin's lymphoma have both shown a response to this novel therapy. Theoretically, hairy cell leukemia and Hodgkin's disease, among other malignancies, could also be targeted. The target malignancies are those that express the high-affinity form of the IL-2 receptor, which seems especially susceptible to the drug, Dr. Murphy said.