Granulocyte-macrophage colony stimulating factor in autologous bone marrow transplantation: augmentation of graft versus tumor effect via antibody dependent cellular cytotoxicity.

Abstract

Several immunomodulatory approaches have been explored with the aim of inducing a graft versus tumor effect (GVT) in autologous bone marrow transplantation (ABMT). Granulocyte-macrophage colony stimulation factor (GM-CSF) has been reported to induce antibody dependent cellular cytotoxicity (ADCC) via stimulation of peripheral blood neutrophils, lymphocytes, and monocytes. We investigated the role of GM-CSF in inducing ADCC via bone marrow (BM) macrophages against murine and human tumor cells both in vitro and vivo. Our data shows that stimulation of murine BM macrophages with GM-CSF induced a potent ADCC against a murine melanoma in vitro. Treatment of tumor bearing mice with a combination of GM-CSF and antibody against melanoma resulted in a significant reduction in the dissemination of melanoma both in a nontransplant as well as in a transplantation setting. Adoptive transfer of BM macrophages obtained from animals undergoing treatment with GM-CSF plus antibody significantly reduced the spread of tumor in secondary recipients; this effect was seen only in mice undergoing bone marrow transplantation. GM-CSF treatment of human BM macrophages induced a significant ADCC against a human melanoma and a lymphoma in vitro, as well as against a human lymphoma implanted in nude mice. Treatment with GM-CSF alone or with antibody alone was ineffective in controlling the dissemination of tumors both in transplantation as well as in nontransplant situations. These observations indicate that treatment with GM-CSF plus tumor specific monoclonal antibodies after ABMT may induce a GVT effect and bring about the eradication of residual disease.