Is it wise to target the late costimulatory molecule OX40 as a therapeutic target?

Abstract

The immune response triggered following pathogen recognition, though required to clear the infection, can be detrimental if it is produced in excess or fails to resolve promptly. Excessive inflammation contributes to infectious and noninfectious pathologies in the gut (such as inflammatory bowel disease), lung (such as bronchiolitis), and in a variety of autoimmune conditions. T cells contribute significantly to pathology during inflammation. Global anti-inflammatory strategies can alleviate the consequences of exuberant inflammation by suppressing T cell activity, but may leave the patient vulnerable to opportunistic infection. More specific therapies aim to suppress only those T cells involved in the disease process, and one such approach is to target late costimulatory molecules. These are not expressed on naïve or resting memory cells. Rather, they have a specific window of expression and their ligation results in the production of abundant inflammatory cytokines. By targeting these molecules, it is hoped that inflammation will reduce, but that therapies will be specific enough to avoid, global immune suppression. This review focuses on the late costimulatory molecule OX40, compare it with other T cell costimulators, and highlight why it is a more suitable target for immune intervention than other immune suppressive strategies.

Kawasaki disease OX40–OX40L axis acts as an upstream regulator of NFAT signaling pathway

“…OX40-OX40L signaling pathway has been shown to play certain curative effect in many animal models (experimental autoimmune encephalomyelitis, rheumatoid arthritis, graft-vs.-host disease, inflammatory bowel disease, and atherosclerosis). [26][27][28][29][30][31][32] Blocking OX40-OX40L axis may be a new target for the management of immune injury of KD.…”

Identification and Characterization of an Agonistic Aptamer Against the T Cell Costimulatory Receptor, OX40

“…OX40 expression has been implicated to play a role in a variety of diseases ranging from inflammatory diseases to the treatment of cancer and has been highlighted as a suitable target for immune intervention because of its temporal expression (Cavanagh and Hussell, 2008). A variety of aptamers that recognize specific cell surface receptors expressed on either B or T lymphocytes (Davis et al, 1998;Dollins et al, 2008;McNamara et al, 2008;Zhang et al, 2009;Zhang et al, 2012) such as CD30, mOX40, and m4-1BB have been identified.…”

Enhancement of the Soluble Form of OX40 and OX40L Costimulatory Molecules but Reduction of the Membrane Form in Type 1 Diabetes (T1D)

“…OX40 is expressed in activated T cells [12], while OX40L is mainly expressed in B lymphocytes, dendritic cells, and macrophage cells [12]. OX40/OX40L signaling acts as a key role in the development and differentiation of some immunological cells, especially T cells [13, 14]. Numerous studies have shown the important role of costimulatory molecules in T1D.…”