Induction of Graft-versus-Leukemia-Activity after Peripheral Blood Progenitor Cell Transplantation (PBPCT)

摘要: Using a murine transplantation model we have investigated the induction of GvL activity with allogeneic peripheral blood progenitor cells (PBPCs). We compared influence PBPC and BM grafts on GvHR leukemic relapse in mice bearing B-lymphoblastic leukemia (A20). Furthermore, evaluated impact T cell depletion risk determined effectiveness ex vivo treatment NK-cell activating cytokines as compensation for loss T-cell derived factors stimulating natural cytotoxicity. Methods: After pretreatment Balb/c (H-2d) recipients 7.5 Gy total body irradiation, 2 × 107 rhG-CSF-mobilized PBPCs syngeneic or MHC-identical DBA were transfered. Selective (TCD) was performed by immunomagnetic purging monoclonal antibody directed against CD3. In some ex-perimental groups, T-cell-depleted incubated 200 U/ml IL-2 100 IL-12 24 hrs. To investigate anti-leukemic vivo, recipient inoculated 1 105A-20 (a Blymphoblastic origin) days prior to PBPCT. Results: The mortality rate due GVHD identical after BMT PBPCT, although contained fourfold amount CD3+ than BMC (61% vs. 15%). rates 80% PBPCT 60% BMT. 34% observed, indicating significantly (p < 0.05)superior GVL TCD antiCD3, incidence GvH-related below 5% but free survival decreased 25% thus similar (17%, p 0.05). When CD3-depleted IL-12, 45% animals remained from leukemia. However, difference statistcally not significant. Our results suggest that stronger effects can be induced ex-vivo activation residual MHC-matched NK-cells does fully compen-sate abrogation GvL-activity CD3-positive T-cells.