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      Donor leukocyte infusion from immunized donors increases tumor vaccine efficacy after allogeneic bone marrow transplantation.

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          Abstract

          Donor T cells play a critical role in mediating both harmful graft-versus-host disease (GVHD) and beneficial graft-versus-tumor effect after allogeneic bone marrow transplantation (BMT). We have recently demonstrated a novel treatment strategy to stimulate specific antitumor activity with preservation of tolerance to host antigens after T cell-depleted allogeneic BMT by vaccination of recipients with irradiated B16 melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor. In this murine system, donor leukocyte infusion from a donor immunized with the recipient-derived B16 vaccines enhanced clinical activity of tumor vaccines without exacerbating GVHD. CD4(+) T cells are essential for this enhancement. In vitro analysis of splenocytes from donor leukocyte infusion donor mice demonstrated that immunization of donors with the recipient-derived B16 vaccines elicited potent T-cell proliferation and cytokine responses specific to B16 antigens. These results demonstrate that immunization of donors with recipient-derived tumor vaccines preferentially induces tumor-specific T-cell responses and that vaccination of both donors and recipients can generate potent antitumor immunity without exacerbating GVHD. This strategy has important implications to prevent recurrence of malignancies after BMT.

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          Author and article information

          Journal
          Cancer Res.
          Cancer research
          0008-5472
          0008-5472
          Feb 01 2002
          : 62
          : 3
          Affiliations
          [1 ] Department of Internal Medicine, University of Michigan Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0942, USA.
          Article
          11830535
          a6bd6584-ce72-48ea-b0fc-4a56b7acd1c9
          History

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