STUDIES OF THE USE OF L-LEUCYL-L-LEUCINE METHYL-ESTER IN CANINE ALLOGENEIC MARROW TRANSPLANTATION

L-leucyl-L-leucine methyl ester (Leu-Leu-OMe) is a lysosomotropic agen t that selectively kills cytotoxic T cells and their precursors, natur al killer cells, and monocytes but not helper T cells or other cells o f hematopoietic origin. In this study, the effects of treatment of bon e marrow and peripheral blood buffy coat with Leu-Leu-OMe on the outco me of allogeneic marrow transplantation were studied in several canine models. Whereas incubation of autologous marrow with Leu-Leu-OMe had no adverse effects on subsequent engraftment, incubation of marrow fro m dog leukocyte antigen (DLA)-identical littermates resulted in a high rate of graft failure. Previous studies have demonstrated that the ad dition of peripheral blood buffy coat allows engraftment of unrelated DLA-nonidentical marrow, and in this study we found that incubation of buffy coat with Leu-Leu-OMe did not alter this graft promoting effect . In a final experiment it was demonstrated that incubation of both ma rrow and peripheral blood buffy coat did not prevent the development o f graft-versus-host disease in recipients of marrow from DLA-haploiden tical littermates. In considering the eventual application of Leu-Leu- OMe in the clinic, these results are less encouraging than those previ ously reported using murine models.