 A recombinant fully human IgG-1 bispecific antibody IBI-315 targeting both PD-1 and or 2 is developed to investigate its anti-tumor efficacy and underlying mechanism in her two positive gastric cancer. IBI-315 crosslinks the physical interaction between her two positive tumor cells and PD-1 positive T cells, leading to enhanced anti-tumor effects compared to each parent antibody or their combination, both in vitro and in vivo mouse tumor models reconstituted with human immune cells using patient-derived xenografts and organoids. IBI-315 also induces the recruitment and activation of immune cells and tumors through GSD-MB mediated pyroptosis, establishing a positive feedback loop of T cell activation and tumor cell killing. GSD-MB is found to be elevated in her two positive gastric cancer cells, providing a rationale for IBI-315's efficacy. IBI-315 is supported as a promising bispecific antibody-based immunotherapy approach for her two positive gastric cancer and preclinical studies. This article was authored by Wu Lin, Yingsi Zhang, Yan Yang, and others. We are article.tv, links in the description below.