Characterization of antileukemia cells' cytotoxic effector function. Implications for monitoring natural killer responses following allogeneic bone marrow transplantation.

We have studied here cytotoxic function of three cloned cell lines--TC12, 48, and 50--derived from circulating lymphocytes that were potentially able to eliminate residual tumor cells in a patient transplanted for treatment of acute lymphocytic leukemia. These cloned cells, which have both phenotypic and functional characteristics of natural killer lymphocytes, were tested in chromium release assays against a panel of 16 uncultured populations of leukemia cells. In addition, their activity was compared with that of cloned and uncloned NK cells from normal individuals. It was found that TC clones induced a much weaker degree of killing against fresh tumor cells compared with conventional NK target cell lines such as K562 or MOLT 4. In addition, there was great heterogeneity in their individual lytic capacity against the various leukemia blasts (TC12, 48, and 50 cells killed in a significant fashion, respectively 7, 1, and 4 of the 16 leukemias), reflecting the functional diversity of normal NK cell populations. Thus, for a fraction of leukemias, there was no correlation between lytic ability of TC cells and that of uncloned lymphokine-activated large granular lymphocytes from normal peripheral blood. Together, these results support the view that direct identification of patients' cytotoxic lymphocytes screened against in vivo relevant tumor cells is necessary to evaluate potentially beneficial immunologic responses in the context of bone marrow transplantation.