Anti-Tumor Necrosis Factor (TNF)

A century ago, the humankind had no idea about tumor necrosis factor (TNF); however, physician William B Cooley was able to demonstrate the principle of anti-tumoral response in vivo as early as in 1891 (1,2). He escalated the idea of anti-tumoral response based on his observation of remission of lesions in patients injected with a mixture of dead Streptococcus pyogenes and Serratia marcescens bacteria (1, 2). Due to the lack of understanding of mechanism behind this observation, it was not properly understood, and was described in a vague term as an immunologic response (1). The advancement in the field of immunology brought a hope to the lost cause, in between late1960 and early 1970 scientists were able to isolate a soluble cytokine and named it tumor necrosis factor (3, 4, and 5). Its discovery in soluble form …show more content…
The most common immunologic responses of this pro-inflammatory multifunctional cytokines includes but is not limited to activation of signaling pathways for cell survival, apoptosis, inflammatory responses, and cellular differentiation (9-11). Primarily TNF are produced by type II transmembrane proteins, which are subdivided in to two groups based on their structure (14).TNF present in long amino-acid form produced by type II transmembrane protein, are known as the membrane bound TNF (mem TNF) (12) . The other commonly seen strucute is soluble TNF (sTNF), which is the product of proteolytic cleavage by the metalloprotease TNF alpha converting enzyme (TACE)(12-14). Regardless of their initial structure, they interchangeably bind to one of the two main receptors (13). However a recent study shows that sTNF more readily binds with TNF-R1 compared to TNFR-2. The binding of TNF with their receptors would normally lead to immunological responses such as apoptosis of the cell