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Fusion Product Delivers Potent Toxin to Malignant Cells

Fusion Product Delivers Potent Toxin to Malignant Cells

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.


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