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Graft-Versus-Host Disease

Transfer of idiotypic protein primed allogeneic marrow grafts elicits potent graft-versus-myeloma effects in mice

Bone Marrow Transplantation volume 27, pages 279–285 (2001)Cite this article

Abstract

The active immunization of bone marrow (BM) donors with myeloma immunoglobulin (Ig) results in an idiotypic T cell response that can be transferred to the recipient. Using a murine model we evaluated the effectiveness, side-effects and underlying mechanisms of this approach. Balb/c (H-2d) mice were given a dose of HOPC-1F myeloma cells secreting the monoclonal IgG2a followed by lethal total body irradiation (7.5 Gy) 2 days later and a subsequent transplantation of 2 × 107 allogeneic MHC-matched DBA/2-derived marrow cells. Donors were pre-immunized with three i.p. injections of HOPCIgG2a or control Ig given with incomplete Freund's adjuvants (IFA) spaced 1 week apart. In some experiments, donor-spleen cells were additionally transferred 2 h post transplant. Injection of HOPC-myeloma led to death of all animals after a median survival time (MST) of 42 days. A lethal dose of TBI followed by transfer of unmanipulated marrow grafts plus splenocytes resulted in moderate antimyeloma effects with 8% of mice achieving long-term survival. Nearly the same results were obtained after transplantation of BM immunized with the control Ig. In contrast, transplantation of marrow grafts from HOPCIgG2a immunized donors exerted a significant GVM effect with 63% long-term survival for more than 180 days. The additional transfer of 2 × 107 immune splenocytes derived from the same donor resulted in even stronger anti-myeloma effects (FFR 87%). No increase in the incidence of severe acute GVHD was observed. In vitro data suggest that allogeneic CD8+idiotype-specific T cells may be the major effector cells. Our results demonstrate that active immunization of the donor with the myeloma-specific Ig can induce powerful graft-versus-myeloma effects after allogeneic BMT. Bone Marrow Transplantation (2001) 27, 279–285.

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Acknowledgements

This work was supported by a grant of the José Carreras Leukämie Stiftung (No. M. Zeis R7) and the Deutsche Krebshilfe (10-1167-ST1).

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Authors and Affiliations

  1. Department of Internal Medicine II, University of Kiel, Germany

    M Zeis & N Schmitz

  2. Division of Hematology/Oncology, University of Leipzig, Germany

    G Hartung & L Uharek

  3. Institute of Immunology, University of Kiel, Germany

    J Steinmann & E Petrela

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  1. M Zeis
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Zeis, M., Steinmann, J., Petrela, E. et al. Transfer of idiotypic protein primed allogeneic marrow grafts elicits potent graft-versus-myeloma effects in mice. Bone Marrow Transplant 27, 279–285 (2001). https://doi.org/10.1038/sj.bmt.1702785

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