Liposome mediated delivery of biological response modifiers (BRM) to macrophages in vivo: A new strategy for therapy of neoplastic disease

Abstract

The disappointing results that have been obtained in efforts to design specific active immunotherapeutic regimens for treatment of neoplastic diseases have led to renewed interest in non-specific host defenses mediated by macrophages. Activated macrophages are capable of recognizing and destroying neoplastic cells without regard to their phenotypic diversity while leaving non-neoplastic cells unharmed. For this reason a significant effort is now underway in many laboratories to identify BRM agents that can stimulate macrophage-mediated tumor cell destruction. Liposomes offer an efficient carrier system for the delivery of BRM agents to macrophages in vivo. After intravenous injection liposomes are taken up by mononuclear phagocytes lining the vascular sinusoids in the liver, spleen and bone marrow and also circulating blood monocytes thus providing an effective mechanism for “targeting” of liposome-encapsulated materials to macrophages in vivo. We have demonstrated that treatment of tumor-bearing animals with liposome-encapsulated BRM produces significant destruction of established metastatic lesions and that the enhanced tumor destruction is mediated by activated macrophages. Although these results are encouraging, the extent of tumor burden at the outset of therapy may limit the clinical utility of this modality. For this reason, therapeutic regimens designed to stimulate macrophage-mediated tumor destruction will almost certainly be used in conjunction with other regimens such as chemo- or radio-therapy which would be used to reduce the tumor burden to a sufficiently low level so that activated macrophages can eradicate the surviving tumor cells. Studies to evaluate multimodality therapy in treatment of metastatic tumors of differing severity in experimental animals are currently in progress.