Rationale for anti-OX40 cancer immunotherapy. (January 2016)

• Record Type: Journal Article
• Authors: Aspeslagh, Sandrine; Postel-Vinay, Sophie; Rusakiewicz, Sylvie; Soria, Jean-Charles; Zitvogel, Laurence; Marabelle, Aurélien
• Is Part Of: European journal of cancer. Volume 52(2016)
• Page Start: 50
• Page End: 66
• Publication Date: 2016-01
• Subjects: OX40 -- CD134 -- Immune checkpoint -- Cancer -- Immunotherapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2015.08.021
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Immune checkpoint blockade with antagonistic monoclonal antibodies (mAbs) targeting B7 immunoglobulin superfamily molecules (CTLA-4, PD-1, and PD-L1) generate long lasting anti-tumour immune responses translating into clinical benefit across many cancer types. However, many patients are primarily resistant to immune checkpoint blockade –based monotherapy and many others will eventually relapse. Therefore, new immunostimulatory targets are needed to overcome primary and secondary resistance to immunotherapy. Besides the B7 co-inhibitory receptors, the tumour necrosis factor receptor superfamily contains many other immune checkpoints, which could become the next generation immunomodulators. Among them stands OX40 (CD134), a co-stimulatory molecule that can be expressed by activated immune cells. Several anti-OX40 agonistic monoclonal antibodies are currently tested in early phase cancer clinical trials. Accumulating preclinical evidence supports their clinical development. However, conflicting results and controversies between in vitro and in vivo data point to the need for comprehensive ancillary studies to be performed in upcoming clinical trials to better understand the mechanism of action of anti-OX40 mAbs-based therapy. Highlights: Combination of anti-OX40 therapy with different anti-cancer agents is very promising. Anti-OX40 therapy does target intratumoural regulatory T-cells. Anti-OX40 should be seen as a novel adjuvant.