Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both granulocyte-macrophage colony-stimulating factor (GM-CSF) and flt3-ligand (FL) induce the development of dendritic cells (DCs). To compare the functional properties of DCs stimulated by these cytokines in vivo, we used retroviral-mediated gene transfer to generate murine tumor cells secreting high levels of each molecule. Injection of tumor cells expressing either GM-CSF or FL resulted in the dramatic increase of CD11c+ cells in the spleen and tumor infiltrate. However, vaccination with irradiated, GM-CSF-secreting tumor cells stimulated more potent antitumor immunity than vaccination with irradiated, FL-secreting tumor cells. The superior antitumor immunity elicited by GM-CSF involved a broad T cell cytokine response, in contrast to the limited Thl response elicited by FL. DCs generated by GM-CSF were CD8alpha- and expressed higher levels of B7-1 and CD1d than DCs cells generated by FL. Injection sites of metastatic melanoma patients vaccinated with irradiated, autologous tumor cells engineered to secrete GM-CSF demonstrated similar, dense infiltrates of DCs expressing high levels of B7-1. These findings reveal critical differences in the abilities of GM-CSF and FL to enhance the function of DCs in vivo and have important implications for the crafting of tumor vaccines.
 ...
PMID:Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. 1086 17

The development of biochemical and genetic schemes to characterize cancer antigens led to the recognition that malignant melanoma frequently evokes a host response. While the generation of brisk T-cell infiltrates in early stage disease is correlated with prolonged survival, host reactions in most cases are insufficient to impede tumor progression. One variable that may limit the potency of the host response against nascent melanoma is the mixture of cytokines present in the tumor microenvironment. In a murine melanoma model, we identified granulocyte-macrophage colony stimulating factor (GM-CSF) as the most potent molecule for augmenting tumor immunity following gene transfer into melanoma cells. Vaccination with irradiated melanoma cells engineered to secrete GM-CSF enhances host responses through improved tumor antigen presentation by recruited dendritic cells and macrophages. Melanoma-specific CD4(+) and CD8(+) T-cells, CD1d-restricted NKT-cells, and antibodies mediate tumor rejection. Initial testing of this immunization strategy in patients with metastatic melanoma revealed the consistent induction of cellular and humoral antitumor responses that provoked the extensive necrosis of distant metastases without significant toxicity.
 ...
PMID:GM-CSF-secreting melanoma vaccines. 1278 95