Abstract 5551: QLS31905, an anti-claudin 18.2/CD3 bispecific antibody for claudin 18.2-positive gastric cancer

Abstract

Abstract Claudin 18.2 is a quadruple transmembrane protein with a complex structure and highly specific expression in gastric and pancreatic cancers. It is suggested that claudin 18.2 is an ideal target for cancer therapy. Anti-claudin 18.2 antibody IMAB362 has achieved remarkable success in the latest clinical trials. Multiple anti-claudin 18.2 monoclonal antibodies and chimeric antigen receptor T-cell therapy targeting claudin 18.2 have also entered phase I clinical trials. CD3 is a receptor that is present on the surface of T cells and is involved in the antigen recognition by T cells as well as in signal transduction. Anti-claudin 18.2/CD3 bispecific antibody can recruit T cells to tumor sites, activating T cells to kill tumor cells with high claudin 18.2 expression to improve efficacy. Here, we describe a new T cell-redirecting antibody (QLS31905) that is bispecific for claudin 18.2 and CD3. QLS31905 showed a potent in vitro cytotoxic activity against claudin 18.2-positive engineered cell lines HEK293-hCLDN18.2 and NCI-N87 CLDN18.2 as well as superior in vivo efficacy in humanized NCI-N87 CLDN18.2 model. Furthermore, QLS31905 was safe and well tolerated in a 4-week repeated dose (up to 10 mg/kg) toxicity study in cynomolgus monkeys. In vitro cytokine release was lower in the QLS31905 group than that in the AMG 910 (another anti-claudin18.2/CD3 bispecific antibody) group. Overall, these data suggested that QLS31905 has similar efficacy to AMG 910 and is safer. QLS31905 may be an effective and clinically valuable treatment for patients with claudin 18.2-positive gastric cancer. Citation Format: Jiahua Jiang, Meimei Si, Xiao Luo, Yun Wu, Yongjun Li, Xiaodan Yan. QLS31905, an anti-claudin 18.2/CD3 bispecific antibody for claudin 18.2-positive gastric cancer [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 5551.