NEW YORK--Researchers at the National Cancer Institute are targeting a T-cell interleukin-2 (IL-2) receptor in an attempt to find an effective treatment for patients with adult T-cell leukemia/lymphoma (ATL), Thomas A. Waldmann, MD, chief of the NCI's Metabolism Branch, said at a symposium sponsored by the New York City-based Cancer Research Institute.
The targeted T-cell receptors under study are "promiscuous," he said; that is, they are shared by the interleukin superfamily that includes IL-2, IL-4, IL-7, IL-9, and IL-15.
No Toxicity to Normal T Cells
The IL-2 receptor is not expressed in resting and activated normal T cells, Dr. Waldmann noted, whereas it is highly expressed in HTLV-1-associated ATL. Thus, tumor cells can be targeted with a radionuclide-labeled monoclonal antibody (MoAb) without targeting normal cells.
In an NCI trial of 19 ATL patients who were given unmodified mouse antibody targeted to the IL-2 receptor, one third of the patients underwent remission, including two who had a complete remission, he said.
In a second trial, in which the MoAb was armed with yttrium-90 (90Y), nine of 18 patients with adult T-cell leukemia had a partial or sustained complete remission.
A new trial is underway employing a humanized MoAb armed with 90Y. Use of the humanized product should allow repeat doses to be given safely without development of immunogenicity.
Dr. Waldmann said that this therapeutic approach may also have potential applications in cutaneous T-cell lymph-oma and in some autoimmune disorders, as well as in the prevention of allograft rejection.
