PEN110 treatment functionally inactivates the PBMNCs present in RBC units: comparison to the effects of exposure to gamma irradiation

BACKGROUND: The presence of WBCs in blood components is the major factor influencing the immunologic consequences of transfusion. Attempts to ameliorate these responses have used WBC reduction or inactivation by ionizing radiation. PEN110 (Inactine, V. I. Technologies) is a chemical that inhibits the replication of infectious pathogens by modifying their nucleic acids. These experiments compared effects of PEN 110 treatment or gamma irradiation on WBC function. STUDY DESIGN AND METHODS: Aliquots of non-WBC-reduced RBC units were treated with PEN 110 or gamma irradiation with appropriate controls, and PBMNCs from these units were tested with in vitro assays. The assays included immunophenotyping, activating T cells with phorbol ester, proliferation of cells in response to mitogens or allogeneic cells, and determining the ability of cells to stimulate proliferative responses and to produce IL-8. DNA fragmentation following PEN110 treatment was examined by PCR and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assays. RESULTS: Treatment of non-WBC-reduced RBC units with PEN110 functionally inactivated WBC in all in vitro assays used. In contrast, while gamma irradiation inhibited proliferation of the WBCs, it did not or only partially inhibited the ability of WBC to function in the other assays. PEN 110, but not gamma irradiation, rapidly induced fragmentation of cellular DNA. CONCLUSION: Because PEN 110 was as effective as gamma irradiation at inhibiting WBC proliferation, FEW 10 treatment could potentially be used to prevent the development of GVHD following transfusion.