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Mycophenolate mofetil does not suppress the graft-versus-leukemia effect or the activity of lymphokine-activated killer (LAK) cells in a murine model

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Abstract

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. Aims: 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 × 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.

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Acknowledgments

This work was done at the Danny Cunniff Leukemia Research Laboratory. We wish to thank the Gabrielle Rich Leukemia Research Foundation; the Cancer Treatment Research Foundation; the Novotny Trust; the Szydlowsky Foundation; The Fig Tree Foundation; and the Ronne & Donald Hess and the Silverstein families for their continuous support of our basic and clinical research.

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  1. Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah–Hebrew University Medical Center, PO Box 12000, 91120, Jerusalem, Israel

    Michael Y. Shapira, Ester Hirshfeld, Lola Weiss, Michael Zeira, Judith Kasir, Reuven Or, Igor B. Resnick & Shimon Slavin

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  1. Michael Y. Shapira
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  2. Ester Hirshfeld
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  3. Lola Weiss
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  4. Michael Zeira
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  7. Igor B. Resnick
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  8. Shimon Slavin
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Correspondence to Michael Y. Shapira.

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Shapira, M.Y., Hirshfeld, E., Weiss, L. et al. Mycophenolate mofetil does not suppress the graft-versus-leukemia effect or the activity of lymphokine-activated killer (LAK) cells in a murine model. Cancer Immunol Immunother 54, 383–388 (2005). https://doi.org/10.1007/s00262-004-0614-9

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  • DOI: https://doi.org/10.1007/s00262-004-0614-9

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