Abstract 2089: Evaluating in vivo efficacy of anti-TSLP antibodies in humanized B-hTSLP/hTSLPR mice

Abstract Expression of the epithelial cytokine, thymic stromal lymphopoietin (TSLP), has been observed across several barrier surfaces and plays a critical role in both physiological and pathological processes. Via T helper (Th) 2 cytokine production, TSLP has been implicated in asthma, atopic dermatitis, inflammatory bowel disease, multiple sclerosis, and chronic obstructive pulmonary disease. This range in which TSLP exerts its effects on inflammatory diseases makes the TSLP/TSLPR axis an attractive therapeutic target. At Biocytogen, we generated a novel TSLP/TSLPR double humanized mouse model that enables in vivo assessment of human anti-TSLP and anti-TSLPR antibodies. In our B-hTSLP/hTSLPR mice, the murine Tslp and Tslpr genes are replaced with the human TSLP and TSLPR genes by homologous recombination. ELISA analysis showed that human TSLP (after induction with calcipotriol) was exclusively detectable in homozygous B-hTSLP/hTSLPR mice compared to wild type mice. Similarly, flow cytometry analysis indicated TSLPR expression was detectable in monocytes, neutrophils, macrophages, total DCs, cDC1, cDC2, Mo-DC and Pre-DC. Percentages of T cells, B cells, NK cells, DCs, granulocytes, monocytes, macrophages, CD8+ T cells, CD4+ T cells and Tregs in homozygous B-hTSLP/hTSLPR mice were comparable to those in the wild type mice, demonstrating that introduction of human TSLP and TSLPR in place of their mouse counterparts did not impair the overall development, differentiation, or distribution of these cell types. Furthermore, using an asthma mouse model via induction with ovalbumin (OVA), we showed that an anti-TSLP antibody (Tezepelumab, synthesized in house) was efficacious in controlling asthma progression in B-hTSLP/hTSLPR mice. Altogether, B-hTSLP/hTSLPR mice are a promising model for preclinical in vivo pharmacodynamic assessment of TSLP antibodies. Citation Format: Shujin Zhang, Yanhui Nie, Jiahui Chang, Veronika Chromikova, Luke (Zhaoxue) Yu, Mari Kuraguchi. Evaluating in vivo efficacy of anti-TSLP antibodies in humanized B-hTSLP/hTSLPR mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2089.