Pharmaceutical perspectives for the delivery of TNF-α in cancer therapy

Abstract

TNF-α is an endogenous signaling protein which controls physiological activities and participates in immune response. It is known to interact with TNF receptors (TNFR), of which have two kinds leading to totally different effects. Binding of TNF-α to TNFR1 can induce either cell proliferation or cell death, i.e., necroptosis, depending on the kinds of protein to which it binds during the signaling cascade. On the contrary, binding of TNF-α to TNFR2 induces only cell death process. TNF-α can also cause antiviral effect by inducing interferon, and can inhibit tumor growth. Moreover, TNF-α helps action of immune cells and it leads to increasement of tumor cell lysis. TNF-α also makes tumor vessels more permeable and induces coagulation and thrombosis in the tumor vessels, which ultimately contribute to antitumor effect. However, TNF-α also has several toxic effects, which include the change in redox status of antioxidant factors, induction of excess inflammation response, and action as pro-inflammatory cytokine of itself. These toxicities need to be considered when developing TNF-α as an anticancer agent. In this review, pharmaceutical approaches to optimize and utilize its antitumor activity of TNF-α as well as to decrease its adverse effect are discussed.