Adoptive immunotherapy with autologous macrophages: current status and future perspectives

Abstract

Adoptive immunotherapy is a treatment modality designed to correct a defective and/or insufficient host defense response to a malignant tumor. Recently, we have developed a large scale technology for the generation of tumor cytotoxic macrophages (MACs) from circulating precursor monocytes. These ex vivo matured and interferon-gamma-activated MACs were used for adoptive transfer in a total of 30 tumor patients by intravenous (n = 12), intraperitoneal (n = 11) and intrahepatic (n = 7) infusion. A biological response to autologous cell transfer was evident from low-grade fever, elevation of C-reactive protein, induction of the coagulation cascade and a rise in interleukin-6 in sera as well as in ascitic fluids. A clinical response was only seen upon intraperitoneal treatment and consisted of palliation of malignant ascites in 3 of 7 patients and in reduction of ascitic tumor markers (CEA, CA125). Future perspectives of MAC therapy in combination with macrophage colony-stimulating factor, bacterial endotoxins and synthetic derivatives as well as monoclonal antibodies against tumor-associated antigens are discussed. Furthermore, the ex vivo manipulation of the MAC system may offer the possibility to use these multifunctional, pleiotropic effector cells not only in malignancy but also for the therapy of complicated opportunistic infections and secondary bone marrow hypoplasia.