Immunotherapy for malignant tumors using combination of allogeneic intra-bone marrow-bone marrow transplantation, donor lymphocyte infusion and dendritic cells

Abstract

We have previously shown that the combination of allogeneic intra-bone marrow-bone marrow transplantation (IBM-BMT) and donor lymphocyte infusion (DLI) using CD4+ cell-depleted spleen cells is effective in suppressing tumor growth, but that this does not induce graft-versus-host disease (GVHD) in mice. In this report, we show that formalin-fixed tumor cell-pulsed dendritic cells (FFTCP DCs) have an additive effect with IBM-BMT plus DLI on the suppression of tumor growth, but that the DCs do not augment GVHD. BALB/c mice, which had been subcutaneously inoculated with Meth A (BALB/c-derived fibrosarcoma), were irradiated at a low dose (5 Gy) and were transplanted with bone marrow cells (BMCs) from C57BL/6 (B6) mice into the bone marrow cavity (IBM-BMT). Simultaneously, the mice were intravenously injected with spleen cells from B6 mice, and subcutaneously injected with FFTCP DCs derived from the bone marrow (BM) of B6 mice. At the point of the induction of DCs from BMCs, formalin-fixed Meth A cells were added into the culture. The mice treated with the combination of FFTCP DCs, IBM-BMT and DLI using CD4+ cell-depleted spleen cells showed smaller tumor sizes and longer survival than the mice treated with IBM-BMT plus FFTCP DCs or IBM-BMT plus DLI using CD4+ cell-depleted spleen cells. These results suggest that the combination of FFTCP DCs, IBM-BMT plus DLI using CD4+ cell-depleted spleen cells has potent anti-tumor effects without showing GVHD.