TNF and melanoma: Indeed, we have previously shown the ligand-directed delivery of a tumor necrosis factor (TNF) transgene to tumors in the setting of human melanoma xenografts [7, 8], a transgenic model of pancreatic neuroendocrine tumors [9], and even in spontaneous native tumors in pet dogs [10] consistently produced antitumor effects without evidence of off-target side effects, a major concern of nontargeted systemic TNF therapy, which is known for severe toxicity [11].