Apoptotic cell injection-induced tolerance preserved graft versus leukemia effect (P2206)

Abstract

Abstract Allogeneic hematopoietic cell transplantation (AHCT) is a curative therapy for hematological malignancies unfortunately limited by graft-versus-host-disease (GvHD) occurrence. We have demonstrated that apoptotic cell injection can favor tolerance due to their immunomodulatory properties and thus increase engraftment and limit GvHD, through TGF-β and regulatory T cell dependent mechanisms. However, since apoptotic cell injection favors tolerance we evaluated whether graft-versus-leukemia (GvL) was preserved. In an experimental mouse model of T cell-depleted bone marrow transplantation (TCD BMT), leukemic A20 luciferase+ cells were injected at d0 and allogeneic donor T cell infusion was given on d6. Apoptotic cells were injected either on d0 or d6. Eradication of leukemic cells was observed in all mice receiving T cells, as attested by tumor growth evaluated by luminescence. Mice not receiving T cells died from leukemia within 27 days. Mice demonstrating GvL also developed GvHD according to Ferrara's score, and only 27% survived at d27. In contrast, 50% of mice receiving apoptotic cells on d0 or d6 survived at d27 and demonstrated long-term GvL with the complete absence of leukemic cell growth. Our data clearly demonstrated that GvHD suppression by apoptotic cell injection does not abrogate GvL activity. Thus, apoptotic cell injection should be considered in clinic to favor engraftment, prevent GvHD, conserving high GvL therapeutic activity.