ANTI-TAC MONOCLONAL WITH RADIOISOTOPE LED TO REMISSION OF T- CELL LEUKEMIA
ANTI-TAC MONOCLONAL WITH RADIOISOTOPE LED TO REMISSION OF T- CELL LEUKEMIA in three of 14 patients, in a National Cancer Institute study reported by NCI researcher Thomas Waldmann at an April 9 press briefing in New York City. The study involved patients with adult T-cell leukemia; three experienced complete remission following treatment with a mouse monoclonal antibody linked to a radioisotope, with no leukemic cells detected since. Waldmann said a total of 10 patients, including the three in remission, "had at least a 95% to 98% reduction in tumor cells, a remission of all skin lesions, a lowering of the very aggressive serum calcium, a return to normal immune function." The remaining four patients who had been failing very aggressive chemotherapy at the time of treatment, had modest responses, he said. One of the complete responders has been in remission for six months and another has been in remission for over a year, NCI said. Waldmann pointed out during his presentation that on average, patients with adult T-cell leukemia generally die within 20 weeks of diagnosis, with or without chemotherapy. The mouse monoclonal used in the study is an anti-Tac (T-cell activated) monoclonal antibody that blocks the IL-2 receptor on the T-cell. By blocking the receptor, the monoclonal prevents the growth factor IL-2 -- which is necessary for the T-cell to stay alive and divide -- from locking onto the T-cell. Waldmann explained that in an earlier trial, NCI researchers used an unmodified monoclonal to treat 20 leukemia patents. He said seven of 20 patients went into remission, three of whom had complete and long-lasting remission. One of the three was treated 28 months ago and is still in complete remission. In the first trial, "a number of the leukemic cells had gone beyond the stage where they could respond to this mouse monoclonal," Waldmann said. So in the current experiment, he and his colleagues "armed the antibody" with radioisotopes, in particular the beta-emitting isotope yttrium 90, in order to kill the cell targeted by the monoclonal. Waldmann noted that there was "modest hematopoietic toxicity" with the isotope-linked monoclonal, which was not observed with the unmodified monoclonal. NCI has recently started a Phase I trial with a humanized version of the mouse monoclonal that involves 12 patients with lymphoma or leukemia other than adult T-cell leukemia. Waldmann noted that patients must be treated in cycles over time and because patients make antibodies to the mouse monoclonals, these monoclonals have been too immunogenic for repeated therapy. He said the humanized monoclonal will enable NCI to study a wider spectrum of leukemias and lymphomas. Hoffmann La-Roche has begun Phase I trials at two centers of its SMART Anti-Tac Antibody, a humanized monoclonal, for treatment of autoimmune disorders, adult T-cell leukemia, T-cell lymphoma and Hodgkin's disease ("The Pink Sheet" Jan. 27, T&G-8). Roche acquired the rights for the monoclonal from Protein Design Labs. Waldmann's presentation was made in conjunction with Bristol- Myers Squibb's annual award of cancer research grants. The NCI researcher received a $50,000 award in recognition of his studies of the immune system that led to new ways to use monoclonal antibodies to treat leukemias, lymphomas, and autoimmune diseases, and to prevent organ and bone marrow transplant rejection. He was nominated by NCI Director Samuel Broder, MD.
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