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.


METHODS
In vitro assays were employed to confirm that PEN110 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 F1 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.


CONCLUSIONS
PEN110 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.
Fast
Loren D
LD
Department of Medicine, Division of Hematology and Oncology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA. Loren_Fast@brown.edu
DiLeone
Gilbert
G
Edson
Clark M
CM
Purmal
Andrei
A
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D003433:Crosses, Genetic; D004353:Drug Evaluation, Preclinical; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007518:Isoantibodies / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D016131:Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016685:Mitomycin / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D037181:Lectins, C-Type; D016685:Mitomycin; D011073:Polyamines; D000099192:CD69 Antigens; C451719:PEN 110