Tumor necrosis factor-alpha (TNF-α), a member of the TNF superfamily, was the first
cytokine to be evaluated for
cancer biotherapy. However, the clinical use of TNF-α is severely limited by its toxicity. Currently, TNF-α is administered only through locoregional drug delivery systems such as isolated limb perfusion and isolated hepatic perfusion. To reduce the systemic toxicity of TNF-α, various strategies have been explored over the last several decades. This review summarizes current state-of-the-art targeted
cancer therapy using TNF-α. Passive targeting, cell-based therapy, gene
therapy with inducible or tissue-specific promoters, targeted
polymer-
DNA complexes,
tumor pre-targeting, antibody-TNF-α conjugate, scFv/TNF-α fusion
proteins, and
peptide/TNF-α fusion
proteins have all been investigated to combat
cancer. Many of these agents are already in advanced clinical trials. Molecular imaging, which can significantly speed up the drug development process, and nanomedicine, which can integrate both imaging and therapeutic components, has the potential to revolutionize future
cancer patient management. Cooperative efforts from scientists within multiple disciplines, as well as close partnerships among many organizations/entities, are needed to quickly translate novel TNF-α-based
therapeutics into clinical investigation.