Amlexanox enhances the antitumor effect of anti-PD-1 antibody

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Cancer immunotherapy using monoclonal antibodies (mAbs) targeting PD-1/PD-L1 signaling offers a novel treatment strategy.
• Limited patient response rates necessitate the identification of agents that enhance immunotherapy efficacy.

Purpose of the Study:

• To identify compounds that potentiate the effectiveness of anti-PD-1 mAb therapy.
• To investigate the mechanism by which amlexanox enhances anti-PD-1 mAb activity.

Main Methods:

• Mixed lymphocyte reaction (MLR) was used to screen for compounds enhancing anti-PD-1 mAb efficacy.
• In vitro assays assessed interferon-gamma (IFN-γ) production and PD-L1 expression.
• In vivo studies utilized a mouse tumor-bearing model to evaluate antitumor effects.

Main Results:

• Amlexanox amplified IFN-γ production in response to anti-PD-1 mAb in MLR.
• Amlexanox induced PD-L1 expression on dendritic cells but not interleukin-2 production by T cells.
• Combination therapy demonstrated enhanced antitumor effects in vivo, increasing expression of IFN-γ, PD-L1, and cytotoxic T cell-related genes within tumors.

Conclusions:

• Amlexanox enhances anti-PD-1 mAb efficacy by modulating dendritic cell function.
• The findings suggest amlexanox acts on dendritic cells to promote T cell-mediated antitumor immunity.
• Amlexanox represents a potential therapeutic agent for combination with PD-1 blockade in cancer treatment.