INTERLEUKIN-12 INDUCED CYTOLYTIC ACTIVITY IN LYMPHOCYTES FROM RECIPIENTS OF AUTOLOGOUS AND ALLOGENEIC STEM-CELL TRANSPLANTS

Interleukin-12 (IL-12) has been reported to enhance the cytolytic acti vity of NK and activated T cells and to induce low levels of lymphokin e-activated killer (LAK) activity in normal human lymphocytes. Therapy with IL-12 has induced tumor eradication in murine models. These obse rvations suggest that IL-12 might have a role as treatment for minimal residual disease following transplantation. To determine whether PBL from recipients of autologous (autoSCT) and allogeneic (alloSCT) bone marrow or peripheral blood stem cell transplants respond to IL-12 with generation of LAK activity, PBL were incubated with IL-12 for 5 days, then tested in a Cr-51 release assay for lysis of Daudi. PBL from 17 normal 'control' individuals were similarly tested and lysis was obser ved in only 3/17 (mean 16.9% of the three). By contrast, PBL from 10/1 2 patients obtained a median of 30 days after autoSCT, exhibited signi ficant IL-12-induced LAK activity (mean lysis, 35.3%, P < 0.005 vs con trols). PBL from 18 of 20 patients tested a median of 44 days after al loSCT also exhibited significant LAK activity (mean lysis, 30.0%, P < 0.005 vs controls). In autoSCT recipients, IL-12 and IL-2 at high conc entrations (1000 U/ml each) were additive for induction of LAK activit y, whereas low, suboptimal concentration of IL-12 (250 U/ml) and IL-2 (1 U/ml) were synergistic in 3/5 experiments. The percentage of PBL ex pressing. IL-12 receptor beta 1 chain (IL-12r beta 1) was higher in st em cell recipients than in normal individuals, P < 0.05. Moreover, a h igher percentage of IL-12r beta 1-positive PBL was associated with gre ater IL-12-induced LAK activity in transplant recipients. These studie s demonstrate that PBL obtained early after stem cell transplantation have a higher percentage of cells expressing IL-12r beta 1 and respond to IL-12 with significantly greater LAK cytotoxicity than PBL from no rmal controls. These results suggest that IL-12 is a potentially attra ctive candidate for study as consolidative immunotherapy after stem ce ll transplantation.