Past, Present and (Foreseeable) Future of Biological Anti-TNF Alpha Therapy

Abstract

Due to the key role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of immunoinflammatory diseases, TNF-α inhibitors have been successfully developed and used in the clinical treatment of autoimmune disorders. Currently, five anti-TNF-α drugs have been approved: infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. Anti-TNF-α biosimilars are also available for clinical use. Here, we will review the historical development as well as the present and potential future applications of anti-TNF-α therapies, which have led to major improvements for patients with several autoimmune diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), psoriasis (PS) and chronic endogenous uveitis. Other therapeutic areas are under evaluation, including viral infections, e.g., COVID-19, as well as chronic neuropsychiatric disorders and certain forms of cancer. The search for biomarkers able to predict responsiveness to anti-TNF-α drugs is also discussed.

Design and Construction of a Synthetic Nanobody Library: Testing Its Potential with a Single Selection Round Strategy

“…The capability of the library to yield specific binders was tested for three protein antigens: tumor necrosis factor (TNF), vascular endothelial growth factor (VEGF) and the glycoprotein complex (GnGc) of Andes virus. Both TNF and VEGF, as well as their receptors, are relevant therapeutic targets in cancer and autoimmune diseases, and several monoclonal antibodies targeting these molecules have been used in the clinics for several years [28][29][30]. Furthermore, several nanobodies specific for VEGF have been reported [31], and very recently (Sept/2022) a trivalent anti-TNF nanobody called ozoralizumab was approved in Japan for the treatment of rheumatoid arthritis [5].…”

Ocular toxoplasmosis following anti-tumour necrosis factor-α therapy combined with oral methotrexate therapy: A case report and review of literature

“…However, TNF-α, released by activated macrophages and T-lymphocytes, plays a significant role in cellmediated immune responses. 1,2 Thus, inhibition of TNF -α with these agents can make the patients susceptible to reactivation of latent infections and the overall risk of various opportunistic infections. 2,3 Toxoplasma gondii is an obligate intracellular protozoan parasite classically known to cause retinochoroiditis with vitritis with a variable clinical spectrum.…”

“…Tumour necrosis factor (TNF)-α is a proinflammatory cytokine implicated in the pathogenesis of various systemic autoimmune disorders. 1 Therapies targeting this proinflammatory cytokine have revolutionized the management of various systemic rheumatological disorders over the past few years. 1 There are several TNF -α blockers available in the market which have shown efficacy in the management of chronic immune-mediated disorders.…”

“…1 Therapies targeting this proinflammatory cytokine have revolutionized the management of various systemic rheumatological disorders over the past few years. 1 There are several TNF -α blockers available in the market which have shown efficacy in the management of chronic immune-mediated disorders. However, TNF–α, released by activated macrophages and T-lymphocytes, plays a significant role in cell-mediated immune responses.…”

“…However, TNF–α, released by activated macrophages and T-lymphocytes, plays a significant role in cell-mediated immune responses. 1,2 Thus, inhibition of TNF – α with these agents can make the patients susceptible to reactivation of latent infections and the overall risk of various opportunistic infections. 2,3…”