Recombinant lnterleukin-2 activates peripheral blood lymphocytes from children with acute leukemia to kill autologous leukemic cells

Abstract

In order to determine if recombinant interleukin-2 (rIL-2) can induce lymphokine-activated killer (LAK) cells able to lyse autologous leukemic cells, we incubated peripheral blood (PB) mononuclear cells from children with acute leukemia with 50 U/ml rIL-2 for 5 days. These PB effector cells were then tested for their ability to lyse autologous leukemic cells in a ⁵¹CR release assay. The PB cells before incubation with rIL-2 showed little or no cytotoxicity for autologous blasts (range, 0 to 12%; mean, 2%). However, after incubation with rIL-2, PB cells from four of five children with acute lymphoblastic leukemia (ALL) at diagnosis or in relapse, and from six of eight children with ALL in remission were able to lyse autologous blasts. The percent lysis (range) was 0 to 69% (mean, 37%) for the former group, and 0 to 113% (mean, 43%) for the latter group. The PB cells from three patients (one in relapse and two in remission) failed to develop LAK activity after incubation with rIL-2. However, in each case cytotoxicity versus K562 was increased after incubation with rIL-2. Furthermore, in a Phase I study of rIL-2 for the treatment of refractory leukemia, a patient was treated with rIL-2 for 3 weeks (nine injections of 3 × 10⁶ U/m² each). Her fresh PB mononuclear cells developed a low level of cytotoxicity (11% lysis) against her autologous blasts during this time. The finding that rIL-2 in vitro and in vivo induces LAK cells with cytotoxicity against autologous leukemic cells provides the rationale for the clinical trial of this agent in the treatment of children with ALL.