F4614

F4614 is a **mutein (mutant protein) of human tumor necrosis factor alpha (TNF-alpha)**, engineered via site-directed mutagenesis to reduce systemic hypotensive toxicity while retaining anti-tumor activity. Key amino acid substitutions include the introduction of a cell-adhesive Arg-Gly-Asp sequence and replacement of arginine at position 29 with valine. F4614 exhibits anti-tumor effects similar to recombinant human TNF-alpha in murine models, significantly inhibits tumor cell growth, upregulates major histocompatibility complex class-I, ICAM-1, and B7-1 expression, induces apoptosis, and stimulates immune cell infiltration upon intratumoral administration. Reduced hypotensive side effects are attributed mainly to its diminished induction of nitric oxide and prostaglandin E2. F4614 has been explored preclinically as a potential systemic and intratumoral immunotherapy for cancers such as hepatocellular carcinoma and sarcoma[1][2][3][4][5].