Abstract 2951: Development of TNFR2, TNFR1 and LTBR humanized mouse model for evaluating anti-human LTBR antibodies

The Lymphotoxin B receptor (LTBR) is primarily expressed on epithelial, stromal, and myeloid cells. LTBR signaling has diverse roles, including regulation of lymphoid organ development, induction of tertiary lymphoid structures (TLS), and promotion of liver regeneration. Recently, the therapeutic strategy of activating LTBR to induce and mature TLS has gained momentum, with LTBR-targeting antibodies now advancing into clinical trials. However, traditional preclinical models generally lack expression of human LTBR, which limits the progress of anti-human LTBR antibody development. To address this, Biocytogen has developed a humanized mouse model expressing TNFR1, TNFR2, and LTBR through Biocytogen proprietary gene editing technology, known as B-hTNFR2/hTNFR1/hLTBR mice. In these mice, humanized TNFR1, TNFR2, and LTBR expression is detected in granulocytes, regulatory T cells, and macrophages, respectively. Testing of anti-human LTBR antibodies in this model has shown effective tumor growth control, underscoring the B-hTNFR2/hTNFR1/hLTBR mouse as a valuable preclinical platform for in vivo evaluation of anti-human LTBR antibodies. Citation Format: Qiurong Wang, Chong Li, Zhixia Li, Zan Zhang, Jiansu Zhang. Development of TNFR2, TNFR1 and LTBR humanized mouse model for evaluating anti-human LTBR antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2951.