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Therapeutic strategies for the costimulatory molecule OX40 in T-cell-mediated immunity
Acta Pharmaceutica Sinica B ; (6): 414-433, 2020.
Article in English | WPRIM | ID: wpr-792999
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.

Full text: Available Index: WPRIM (Western Pacific) Language: English Journal: Acta Pharmaceutica Sinica B Year: 2020 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: English Journal: Acta Pharmaceutica Sinica B Year: 2020 Type: Article