GM-CSF-secreting melanoma vaccines

摘要: The development of biochemical and genetic schemes to characterize cancer antigens led the recognition that malignant melanoma frequently evokes a host response. While generation brisk T-cell infiltrates in early stage disease is correlated with prolonged survival, reactions most cases are insufficient impede tumor progression. One variable may limit potency response against nascent mixture cytokines present microenvironment. In murine model, we identified granulocyte–macrophage colony stimulating factor (GM-CSF) as potent molecule for augmenting immunity following gene transfer into cells. Vaccination irradiated cells engineered secrete GM-CSF enhances responses through improved antigen presentation by recruited dendritic macrophages. Melanoma-specific CD4+ CD8+ T-cells, CD1d-restricted NKT-cells, antibodies mediate rejection. Initial testing this immunization strategy patients metastatic revealed consistent induction cellular humoral antitumor provoked extensive necrosis distant metastases without significant toxicity.