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**TNFerade + fluorouracil + cisplatin** is a **combination regimen for cancer therapy** comprising three agents: - **TNFerade**, an adenovector-based gene therapy delivering the gene encoding **tumor necrosis factor-alpha (TNF-α)** under the control of the chemo-radiation-inducible Egr-1 promoter. Upon intratumoral injection and activation by radiation or certain chemotherapies, TNFerade induces local production of TNF-α, resulting in potent anti-tumor effects. Mechanism highlights include immune activation (notably CD8+ T cell induction) via interferon-beta, suppression of metastases, and synergy with radiation or chemotherapeutic agents. - **Fluorouracil (5-FU)**, a small molecule antimetabolite that inhibits thymidylate synthase, leading to inhibition of DNA synthesis and cell death in rapidly dividing tumor cells. - **Cisplatin**, a small molecule platinum-based chemotherapeutic agent that crosslinks DNA, triggering apoptosis in cancer cells. This combination is explored for the treatment of various solid tumors, aiming to maximize localized destruction of tumor tissue and reduce systemic toxicity. TNFerade has primarily been investigated in combination with radiation and cytotoxic agents in preclinical and early-phase clinical studies[1][2][3][4].
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