rHuGM-CSF stimulates the proliferation and differentiation of multiple hematopoietic progenitor cells in the myeloid lineage and activates or augments many of the functional activities of mature neutrophils, monocytes/macrophages, and dendritic cells, enhancing host defenses against a broad spectrum of invading microorganisms. These properties have greatly expanded the possible therapeutic benefits of the cytokine in a wide variety of settings (Table 4), particularly those in which prevention of infection is desirable. The drug may be useful as prophylaxis or adjunctive treatment of bacterial or fungal infections in immunocompromised individuals, including cancer patients receiving myelosuppressive chemotherapy and patients with advanced HIV infection. In addition, exposure to rHuGM-CSF has recently been shown to reduce the susceptibility of macrophages to infection by HIV Sargramostim is being evaluated as a vaccine adjuvant against infectious diseases and malignancies and as immunotherapy in the treatment of various malignancies, including melanoma and neuroblastoma. Based on the increasing variety of biologic effects being attributed to endogenous GM-CSF, additional clinical uses for sargramostim and molgramostim are under investigation. Because rHuGM-CSF has been shown to stimulate the migration and proliferation of endothelial cells and local application of rHuGM-CSF in animal studies has shown faster wound healing times, clinical trials have evaluated rHuGM-CSF in patients susceptible to mucosal damage, such as mucositis, stomatitis, and diarrhea, and those with nonhealing wounds and ulcers. It is likely that the future will see application of rHuGM-CSF in a variety of settings beyond those classically associated with myelosuppression.
ASJC Scopus subject areas
- Cell Biology