Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity

• 来源期刊: 药学学报（英文版）
• 关键词: OX40 CD4+ CDS+ Treg Autoimmunity diseases Cancer immunotherapy
• 年，卷（期）: 2020,（3）
• 页码范围: 414-433
• 页数: 20页
• 语种: 英文

摘要

The T cell co-stimulatory molecule OX40 and its cognate ligand OX40L have attracted broad research interest as a therapeutic target in T cell-mediated diseases.Accumulating preclinical evidencehighlights the therapeutic efficacy of both agonist and blockade of the OX40-OX40L interaction.Despite this progress,many questions about the immuno-modulator roles of OX40 on T cell function remain unanswered.In this review we summarize the impact of the OX40-OX40L interaction on T cell subsets,including Thl,Th2,Th9,Th17,Th22,Treg,Tfh,and CD8+ T cells,to gain a comprehensive understanding of anti-OX40 mAb-based therapies.The potential therapeutic application of the OX40 -OX40L interaction in autoimmunity diseases and cancer immunotherapy are further discussed;OX40 -OX40L blockade may ameliorate autoantigen-specific T cell responses and reduce immune activity in autoimmunity diseases.We also explore the rationale of targeting OX40-OX40L interactions in cancer immunotherapy.Ligation of OX40 with targeted agonist anti-OX40 mAbs conveys activating signals to T cells.When combined with other therapeutic treatments,such as anti-PD-1 or anti-CTLA-4 blockade,cytokines,chemotherapy,or radiotherapy,the anti-tumor activity of agonist anti-OX40 treatment will be further enhanced.These data collectively suggest great potential for OX40-mediated therapies.