IMMUNOTHERAPEUTIC ASPECTS OF ALLOGENEIC PERIPHERAL PROGENITOR CELLS

In a newly developed murine model of allogeneic peripheral progenitor transplantation (PBPCT) we investigated the immunotherapeutic potentia l of allogeneic peripheral stem cells, The following topics were addre ssed by our experiments: (1) comparison of the graft-versus-leukemia e ffect exerted by allogeneic PBPCT compared to allogeneic BMT; (2) the influence of T-lymphocytes on GVL activity; (3) the possibility to enh ance the GVL activity of allogeneic PBPCT grafts by ex vivo cytokine i ncubation, Balb/c mice received cells of the syngeneic B-lymphatic leu kemia A20 2 days prior to TBI (7.5 Gy) and the respective graft. The r ecipients received allogeneic bone marrow grafts or allogeneic periphe ral progenitor cells obtained after mobilization of the donors (DBA/2) with either G-CSF in a dose of 250 mu g/kg/day for 5 days. In some ex periments T lymphocytes were removed by immunomagnetic depletion with CD3-coated beads. An additional group received T cell-depleted and IL- 2/IL12-activated PBPCT grafts. The antileukemic activity of an allogen eic PBPCT graft was significantly greater than the antileukemic activi ty of an allogeneic BMT graft of the same size. Relapse rates were 80% in syngeneic PBPCT, 60% after allogeneic BMT and 34% after allogeneic PBPCT, This rise in antileukemic activity is not accompanied by a ris e in GVHD mortality. Depletion of T lymphocytes by CD3-coated beads re sulted in a nearly complete loss of the GVL activity with a relapse ra te of 75%, Incubation of the T-depleted graft with IL-2 and IL-12 to e nhance NK-based GVL activity has only limited success after MHC-matche d transplantation with a relapse rate of 55%, Allogeneic PBPC exert a pronounced antileukemic effect. After MHC-matched PBPCT, this GVL effe ct resides mostly on the T cells of the graft. Ex vivo activation of T cell-depleted grafts by IL-2 and IL-12 is accompanied by an only limi ted reduction of relapse rate. PBPC are a valuable modality for primar y transplantation in situations with high risk of relapse and for the treatment of relapse after BMT.