We have studies 45 cases of T cell and myeloid leukemia trying to further characterize them. In 15 cases, these cells respond to treatment with IL-2, in that they develop the ability to kill tumor cells. Their phenotype changes to resemble that of a more mature T cell. Using these cases, we have studied the role of the T cell receptor in generation of cytotoxic activity. In one case, IL-2 induced a proliferation of cells utilizing TCR gamma delta. We demonstrated that this TCR was functional in that anti-CD3 stimulated an elevation of intracellular (CA2+) and augmented MHC-unrestricted cytalysis. Trigerring of the TCR gamma delta in this case leads directly to release of cytolytic granule enzymes. In studying the role of IL-2 in this process, we observed that the changes we recorded following IL-2 were transduced solely via the P75 IL-2 binding protein and not the P55 (TAC) protein. Based on these findings, we have begun a clinical protocol, in collaboration with DRS. Poplack and Kirsh, to study the effectiveness of rIL-2 in vivo as a treatment for immature T cell malignancies.
