A potent anti-TSLP mAb reduces type 2 inflammation in primary COPD epithelial cells

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Introduction: The importance of type 2 immunity in chronic obstructive pulmonary disease (COPD) pathogenesis is increasingly recognized. Thymic stromal lymphopoietin (TSLP), a proinflammatory cytokine released by bronchial epithelial cells (BEC), activates type 2 immunity. The effects of TSLP blockade are largely unknown in COPD. Aim: To evaluate the effects of a novel anti-TSLP antibody, solrikitug, on human primary BEC from participants with and without COPD. Methods: Primary human BEC were isolated from COPD patients (n=5) and healthy controls (n=6) undergoing research bronchoscopy. Cells were cultured as submerged monolayers, pretreated for 16 hours with or without solrikitug (25 µg/ml and 250 µg/ml), followed by 10 ng/ml interleukin 13 (IL-13). Eotaxin-3 and TSLP were measured in supernatants by ELISA after 48 hours. Results: IL-13 significantly increased eotaxin-3 and TSLP levels relative to baseline (p=0.006 for both). Solrikitug significantly attenuated IL-13 induced eotaxin-3 and TSLP secretion by BEC (p=0.006 for both). The attenuation rate with 25 µg/ml of Solrikitug group was ~40% for both eotaxin-3 and TSLP. The results were similar for BECs from COPD and control groups. Conclusions: Solrikitug significantly reduced markers of type 2 inflammation in BECs of both COPD and non-COPD participants. These findings support the potential therapeutic role of solrikitug in patients with COPD who have enhanced type 2 immunity. erj;66/suppl_69/PA4579/F1 F1 F1

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