REVERSAL OF ACUTE MYELOGENOUS LEUKEMIA IN HUMANIZED SCID MICE USING ANOVEL ADOPTIVE TRANSFER APPROACH

Advanced human malignancies cannot be permanently cured by adoptive tr ansfer of autologous lymphokine-activated killer (LAK) cells. Moreover , administration of high doses of IL-2 to maintain LAK activity in viv o is associated with severe toxicity. In this study, we tested the ant i-tumor efficacy of a uniquely potent MHC non-restricted human killer T cell clone (TALL-104) in humanized severe combined immunodeficient ( SCID) mice bearing acute myelogenous leukemia (AML). We show that, in appropriate experimental conditions, TALL-104 cells could effectively reverse the aggressive growth of the myelomonocytic leukemia cell line U937 in SCID mouse tissues, leading to complete abrogation of AML. A single transfer of TALL-104 cells at the time of tumor challenge in co mbination with recombinant human (rh) IL-12(1 mu g/d) prolonged signif icantly the life of the mice. However, eradication of leukemia, as mon itored both clinically and by PCR, was achieved by repeated injection of the effecters at close intervals. Complete cure was obtained also u pon transfer of lethally irradiated (non-proliferating) TALL-104 cells together with low doses of rh IL-2 (100 U/d). Most notably, of the mi ce that received multiple transfers of TALL-104 cells without cytokine s in an advanced disease stage, 50% were clinically cured, and 50% sur vived significantly longer. The potential of TALL-104 cells as an effe ctive and safe leukemia purging agent is discussed.