Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity.
10.1016/j.apsb.2019.08.010
- Author:
Yu FU
1
;
Qing LIN
1
;
Zhirong ZHANG
1
;
Ling ZHANG
1
Author Information
1. Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, College of Polymer Science and Engineering, West China School of Pharmacy, Sichuan University, Chengdu 610064, China.
- Publication Type:Journal Article
- Keywords:
Autoimmunity diseases;
CD4+;
CD8+;
Cancer immunotherapy;
OX40;
Treg
- From:
Acta Pharmaceutica Sinica B
2020;10(3):414-433
- CountryChina
- Language:English
-
Abstract:
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 evidence highlights 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 Th1, 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.
