The goal of the proposed research is to develop a model of allogeneic bone marrow transplantation to treat the BCL1 leukemia/lymphoma (IgM, lambda B cell tumor) in BALB/c and BALB/c x C57BL/Ka F1 hybrid mice. Previous studies showed that a low density fraction of bone marrow and spleen cells from C57BL/Ka donors (H-2b) transplanted into lethally irradiated BALB/c (H-2d) or F1 hybrid hosts injected with 107 tumor cells was effective in "curing" the leukemia. The transplant inoculum induced little or no acute graft versus host disease (GVHD), but graft versus leukemia (GVL) activity was preserved. However, hosts with frank leukemia (white blood cell count > 20,000 cells/mm) were not effectively treated with this regimen. In order to increase the anti-leukemic activity of the transplant, we propose to immunize the transplant donors to the BCL1 idiotype protein, and to monitor the anti-idiotype antibody response in the hosts. We will also study the cellular basis of GVHD and GVL activity in this model, by examining these functions in donor CD4+ and CD8+ T cells as well as searching for tumor specific cytolytic T cells in the host. In addition, we will study an MHC matched model of transplantation in which cells from (H-2d) B10.D2 donors immunized with the BCL1 idiotype are transplanted into BALB/c (H-2d) hosts bearing the BCL1 leukemia.
NIH ExPorter
NIH ExPorter