MEMPHIS, Tenn., October 3, 1997 -- New cancer treatments could result from the discovery reported today in Science of a pathway in blood cells through which signals triggering the immune system response may be transmitted from the lymphocyte cell surface to its nucleus.
In making the discovery, researchers at St. Jude Children's Research Hospital located a new protein receptor on the lymphocyte cell surface, identifying it as a member of the important Tumor Necrosis Factor Receptor superfamily, members of which have become targets of a growing number of promising cancer treatments.
Receptors are molecules, often proteins, located on the surface of the cell that recognize and bind with specific molecules outside the cell, transmitting a signal to the interior of the cell.
The new receptor, called TACI (transmembrane activator and CAML-interactor), was also found by the researchers to interact physically with a protein inside the cell, called CAML (calcium-modulator and cyclophilin ligand). CAML, discovered by St. Jude researchers in 1994, triggers an influx of calcium which the cell nucleus reads as a key signal required for initiating the early immune response.
"Our research began with the observation that use of the transplant rejection inhibitor drug cyclosporin, used in bone marrow transplants for leukemia patients, blocked a calcium dependent signal from the T-cell receptor responsible for T-cell activation. Essentially working from the lymphocyte nucleus outward we first discovered CAML, then TACI and that TACI is part of the Tumor Necrosis Factor Receptor superfamily," said Richard Bram, M.D., Ph.D., leader of the St. Jude research team.
"We believe that these two proteins, acting in concert, help instruct lymphocytes to proceed with the program of cell activation and division. Abnormal expression or function of these proteins may contribute to the growth of leukemia cells, which are lymphocytes that grow inappropriately. Now, we are in a position to use knowledge of this signaling pathway to begin to look for more effective cancer treatments, particularly for leukemia and lymphoma patients, many of whom are children," added Bram.
St. Jude Children's Research Hospital, in Memphis, Tenn., was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is primarily supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.
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Journal
Science