Y101S

**Y101S** is a preclinical immune-stimulating antibody conjugate designed to co-localize dual checkpoint blockade and innate immune activation within tumors. It consists of the TGF-β/PD-L1 bispecific antibody YM101 conjugated through a cleavable linker to MSA-2, a small-molecule STING agonist. Y101S blocks TGF-β and PD-L1 signaling while enabling intracellular release of MSA-2 to activate STING, induce type I interferon signaling and CXCL16 expression, and promote recruitment and activation of CXCR6-positive cytotoxic CD8-positive T cells. In murine breast cancer, colorectal cancer, and melanoma models, it showed antitumor activity, survival benefit, immune-memory effects, and no detectable systemic toxicity in the reported preclinical studies. ([nature.com](https://www.nature.com/articles/s41467-026-69456-3))