TNF and clinical
The application of TNF in the treatment of tumors has started clinical phase II trials. It can also be combined with IL-2 to treat tumors. Currently, it is believed that the efficacy of systemic drugs is not as good as that of local drugs. The latter, such as intralesional injection, has high local concentration and less side effects. In recent years, TNF gene therapy has been used for clinical validation of melanoma and other tumors. It is worth noting that TNF is related to the occurrence of some clinical diseases.
(1) Septic shock: It is currently believed that disseminated intravascular coagulation and toxic shock caused by Gram-negative bacilli or meningococcus are caused by bacterial endotoxin that stimulates the body to produce excessive TNF-α, causing fever and severe damage to the heart and adrenal glands. , respiratory and circulatory failure, and even cause death, the level of TNF is positively correlated with mortality. The pathogenesis may be that TNF stimulates endothelial cells, leading to inflammation, tissue damage and coagulation. TNF is also an important factor in acute liver necrosis. Peripheral blood cells in viral fulminant liver failure induce TNF, and the activity of IL-1 increases, which is related to the severity of the disease. The mechanism of TNF-mediated endotoxic shock is still unclear. It is believed that TNF can promote the production of prothrombin active substances and inhibit endothelial cell thrombin to regulate toxic shock. TNF antibodies (antisera or monoclonal antibodies) are effective in preventing lethal endotoxic shock in mice, rabbits and baboons. The application of anti-TNf McAb in the treatment of sepsis and septic shock has entered the phase III clinical trial, and the anti-TNF chimeric antibody in the treatment of bacterial infection has also started the phase I clinical trial.