Induction of cytotoxic lymphocyte subsets against leukemia by stimulation with AML blasts.

Although the application of interleukin-2 (IL-2) activated lymphocytes in immunotherapy of acute myelogenous leukemia (AML) is of therapeutic interest, the high resistance of AML blasts to lymphocyte lysis may represent an obstacle to this type of therapy. However, our data shows that the leukemia resistance can be conquered by concomitant culture of lymphocytes with IL-2 and AML blasts. This approach induces not only leukemia-directed cytotoxic cells, but also promotes their growth. Additionally, multiple cytotoxic lymphocyte populations with leukemia lytic activity are induced in AML/IL-2 cultures. These include natural killer (NK) cells and subsets of T cells with both the major histocompatibility complex (MHC)-restricted and MHC-nonrestricted cytotoxic function. Thus, this protocol, which is conducive to general stimulation of cellular immune responses against leukemia, may enhance the benefits of lymphocyte therapy.