L-LEUCYL-L-LEUCINE METHYL ESTER TREATMENT OF DONOR LYPMHOCYTE INFUSIONS IN HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS

摘要

The present invention relates to a method of inhibiting graft-versus-hostdisease in allogeneic hematopoietic stem cell transplant (HSCT) patients byusing L-leucyl-L-leucine methyl ester (LLME) to eliminate selective cytotoxicT cells in donor lymphocyte infusions (DLI). LLME has been shown to inhibitGVHD in animal models by selectively inducing apoptosis in natural killercells and cytotoxic T cells. The application of LLME to the human clinicalHSCT situation, however, has been hampered by HSC toxicity when useparatedmarrow is treated at the concentrations necessary to purge GVHD-inducing Tcells prior to infusion. In the present invention, this problem iscircumvented by the LLME ex vivo treatment of DLI administered followingtransplantation of T cell-depleted HSC. In this setting, the effects of LLMEon HSC contained within the DLI are irrelevant for clinical outcome. Inanother embodiment, the risk of toxicity to the stem cell population isavoided by ex vivo LLME treatment of donor lymphocytes after separation ofCD34+ stem cells and then co-administration of the LLME-treated donor CD34-fraction and the untreated CD34+ stem cells.