INDUCTION BY INTERLEUKIN-7 OF LYMPHOKINE-ACTIVATED KILLER ACTIVITY INLYMPHOCYTES FROM AUTOLOGOUS AND SYNGENEIC MARROW TRANSPLANT RECIPIENTS BEFORE AND AFTER SYSTEMIC INTERLEUKIN-2 THERAPY

Therapy with recombinant lymphokines after autologous bone marrow tran splantation (ABMT) is being explored as a way to prevent relapse. Lymp hokine therapy may exert an antitumor effect through a variety of mech anisms, including the induction of lymphokine-activated killer (LAK) c ell cytotoxicity. We tested the ability of interleukin-7 (IL-7) to ind uce LAK cytotoxicity in peripheral blood mononuclear cells (PBMC) from healthy subjects and from patients early after ABMT. LAK activity was defined as lysis of Daudi by PBMC after incubation with IL-7 at 10 to 100 ng/mL or IL-2 at 1000 U/mL. PBMC from four healthy subjects were cultured with either IL-7 or IL-2. IL-7 induced LAK activity in two of the four, whereas IL-2 induced LAK activity in all four. The median p ercent lysis (effector-to-target ratio [E:T] 40:1) with IL-7 (23%) was lower than with IL-2 (67%). PBMC were obtained from 15 patients 27 to 84 days after autologous (n=13) or syngeneic (n=2) bone marrow transp lantation (BMT) and tested for IL-7-induced LAK activity. Eleven exhib ited significant activity (10% to 77% lysis at E:T 40:1). In contrast to the results in PBMC from normal subjects, in PBMC from ABMT patient s IL-7 induced LAK activity of a magnitude similar to that induced by IL-2. Studies were also performed on PBMC from eight patients who had received IL-2 after ABMT (3.0x10(6) U/m(2)/d) for 4 days by continuous intravenous (IV) infusion. In seven of the eight patients, IL-7 induc ed significant LAK activity, which was higher than that seen in PBMC f rom ABMT patients who had not received IL-2. Thus, IL-7 reproducibly i nduced significant LAK activity in cells obtained early after autologo us or syngeneic BMT. Indeed, such LAK activity was comparable quantita tively to that induced by IL-2. Finally, IL-7 induced an even greater LAK activity in vitro in PBMC obtained after ABMT and preactivated in vivo by IL-2 therapy. The results suggest that IL-7 may have a potenti al immunotherapeutic role, alone or with IL-2, after ABMT.