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Donor Leukocyte Infusion from Immunized Donors Increases Tumor Vaccine Efficacy after Allogeneic Bone Marrow Transplantation¹

Departments of Internal Medicine and Pediatrics, University of Michigan Cancer Center, Ann Arbor, Michigan 48109-0942 [T. T., K. P. L., J. L. M. F.]; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida 32610-0275 [C. L.]; and Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115 [G. D.]

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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