Mycophenolate mofetil does not suppress the graft-versus-leukemia effect or the activity of lymphokine-activated killer (LAK) cells in a murine model.
BACKGROUND
Graft-versus-leukemia (GVL) effect is an essential component in the course of allogeneic stem cell transplantation (SCT). However, both prevention and treatment of established graft-versus-host disease (GVHD), including with drugs such as cyclosporine, can suppress GVL effects. Mycophenolate mofetil (MMF) is becoming a standard of care in SCT recipients for better prevention of GVHD as well as for promoting stem cell engraftment.


OBJECTIVE
To evaluate the effect of MMF, an immunosuppressive drug increasingly used for prevention of GVHD, on disease recurrence following SCT in a preclinical animal model. Since GVL effects may be also induced by alloreactive natural killer (NK) cells, the goal was to investigate the effects of MMF on the activity of lymphokine-activated killer (LAK) cells.


METHODS
MMF was administered by daily intraperitoneal injection starting at day 1 post-SCT. Cytotoxic LAK activity was measured by 5-h 35S-release assay, and GVL was tested by the appearance of BCL1 leukemia in a semi-mismatched (C57BL/6 donors to [BALB/c x C57BL/6] F1 recipients) murine model.


RESULTS
A dosage regimen of 28-200 mg/kg per day MMF had no negative effect on either cytotoxic LAK activity or GVL (as measured by finding of leukemic cells in recipient spleen by PCR or the appearance of clinical leukemia with adoptive transfer).


CONCLUSIONS
These results suggest that MMF does not impair GVL effects or reduce LAK cell activity in mice.
Shapira
Michael Y
MY
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, PO Box 12000, 91120, Jerusalem, Israel. shapiram@hadassah.org.il
Hirshfeld
Ester
E
Weiss
Lola
L
Zeira
Michael
M
Kasir
Judith
J
Or
Reuven
R
Resnick
Igor B
IB
Slavin
Shimon
S
D000818:Animals; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D020544:Graft vs Leukemia Effect / Q000187:drug effects*; D016219:Immunotherapy, Adoptive; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000276:immunology* / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000637:transplantation; D015448:Leukemia, B-Cell / Q000276:immunology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D004791:Enzyme Inhibitors; D007376:Interleukin-2; D019938:Cyclin D1; D009173:Mycophenolic Acid