Inhibition of murine GVHD by PEN110 treatment

BACKGROUND: The presence of WBCs in blood components is the primary factor influencing the immunologic consequences of transfusion, such as GVHD and alloimmunization. Depletion or inactivation of WBCs can reduce the deleterious responses. Because treatment with PEN110 (Inactine, V. I. Technologies), an ethyleneimine derivative that disrupts nucleic acid replication, was shown to inactivate in vitro human PBMNC function, the ability of PEN110-treated cells to trigger GVHD or alloantibodies was studied with in vivo murine models. STUDY DESIGN AND METHODS: In vitro assays were employed to confirm that PEN 110 treatment inactivated murine splenocyte function as effectively as for human PBMNCs. In vivo experiments in mice examined the ability of PEN110-treated cells to induce GVHD responses in a parent into F, hybrid GVHD model, to induce alloantibodies, to stimulate MHC-restricted cytolytic T lymphocyte responses, and to persist after injection. RESULTS: PEN110-treated murine splenocytes did not respond or induce responses in any in vitro or in vivo assay. The PEN110-treated cells were eliminated from blood and secondary lymphoid organs much more rapidly than were untreated cells. CONCLUSION: PEN 110 treatment prevents the development of GVHD and alloantibody production following WBC transfusion in a murine model system, supporting the continued development of PEN110 treatment of cellular blood components as an alternative to gamma irradiation for the prevention of GVHD.