Comparative efficacy and safety of chimeric and recombinant anti-TNF-α mAbs

Abstract

TNF-α has been known since 1985. It is a multifunctional proinflammatory cytokine, synthesized mainly by monocytes and macrophages. Since its discovery, many studies have been conducted that have proven that it provides homeostatic function and regulates many biological processes in the body. Violation of its regulation in humans is associated with the development of many autoimmune diseases. The intensive studies that led to the understanding of its polyfunctionality and its role in the immunopathogenesis of a number of diseases served as the basis for the development of anti-cytokine therapy with monoclonal antibodies. In 1975, a technique for producing such antibodies was developed. The first antibodies against TNF-α obtained were chimeric, consisting of 30% mouse protein. Because of this feature, drugs based on chimeric antibodies had immunogenicity, which was manifested in the formation of antibodies to the drug, which led to a decrease in their effectiveness. To reduce immunogenicity, scientists in 1990 created the first fully human monoclonal antibody based on a technology called phage display. This is how adalimumab was born, the first fully human multi-clonal antibody to TNF-α. Humira® (adalimumab) is currently considered a widely studied drug from the group of TNF-α inhibitors, with a good safety and efficacy profile. The article presents current data that demonstrate that the drug significantly improves the course of diseases such as rheumatoid and psoriatic arthritis, and will allow for long-term remission in Crohn’s disease.

Keywords

• tnf-α blockers
• adalimumab
• rheumatoid arthritis
• crohn’s disease
• chimeric antibodies
• humanised antibodies