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Donor Lymphocyte Infusions

Allogeneic cell-mediated immunotherapy of leukemia with immune donor lymphocytes to upregulate antitumor effects and downregulate antihost responses

Bone Marrow Transplantation volume 32, pages 495–504 (2003)Cite this article

Summary:

Donor lymphocyte infusion mediates most effective graft- versus-leukemia (GVL) effects following induction of host-versus-graft tolerance by transplantation of donor stem cells. This study was designed to maximize GVL effects across both major (MHC) and minor (mHgs) histocompatibility barriers in recipients inoculated with murine B-cell leukemia (BCL1), using specifically immune donor lymphocytes. GVL effects were induced with donor spleen cells from mice immunized across MHC or mHgs barriers with BCL/1 cells or normal BALB/c spleen cells. Our data suggest that spleen cells from donor mice immunized against murine B-cell leukemia of BALB/c origin, or to a lesser extent against normal host alloantigens, induce better therapeutic GVL effects with less great-versus-host disease (GVHD) across both mHgs and MHC. The cytokine profile of effector cells inducing predominantly GVL effects with reduced GVHD across MHC and mHg barriers consisted preferentially of upregulated IFN-gamma, IL-2, IL-10 and IL-12 in donors, implying a Th-1 to Th-2 cytokine shift. We hypothesize that immunotherapy with immune donor lymphocytes sensitized in vivo or in vitro with allogeneic tumor cells or normal host cells together with allogeneic BMT may provide an effective approach for amplifying GVL effects, while reducing procedure-related morbidity and mortality due to uncontrolled GVHD.

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Acknowledgements

We wish to thank the Danny Cunniff Leukemia Research Laboratory, the Gabrielle Rich Leukemia Research Foundation, the Cancer Treatment Research Foundation, the Novotny Trust, the Szydlowsky Foundation, the Fig Tree Foundation, and Ronne & Donald Hess for their continuous support of our ongoing basic and clinical research.

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  1. L Schuger

    Present address: Department of Pathology, Wayne State University, School of Medicine, Detroit, MI, 48202, USA

Authors and Affiliations

  1. Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah University Hospital, Jerusalem, Israel

    Y H Ji, L Weiss, M Zeira, A Abdul-Hai, S Reich, L Schuger & S Slavin

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Ji, Y., Weiss, L., Zeira, M. et al. Allogeneic cell-mediated immunotherapy of leukemia with immune donor lymphocytes to upregulate antitumor effects and downregulate antihost responses. Bone Marrow Transplant 32, 495–504 (2003). https://doi.org/10.1038/sj.bmt.1704150

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