AtaGenix December 2025 Literature Collection: Advancing Life Sciences Through Cutting-Edge Research Support

Fibrosis caused by neurogenic bladder (NB) is the primary cause of irreversible bladder damage. Using single-cell RNA sequencing, researchers identified a rapidly expanding Itga8+ fibroblast subpopulation in NB fibrosis. Fn1 secreted by Trem2+ macrophages binds to Itga8 on the fibroblast surface, driving fibroblast activation through the FAK/RhoA/ROCK signaling pathway. In vivo experiments — including macrophage depletion, local Itga8 knockdown, and fibroblast-specific Itga8 knockout — validated that targeting Itga8 effectively reduces bladder collagen deposition and improves voiding function, offering a new therapeutic target for NB fibrosis.

Nectin-4 is highly expressed in various solid tumors and is an effective target for antibody-drug conjugates (ADCs), but its application in CAR-T cell therapy remains underexplored. This study developed a low-affinity Nectin-4-specific CAR (CT293) that shows reduced sensitivity to soluble Nectin-4 and low antigen density, demonstrating excellent antitumor activity in preclinical models. A first-in-human clinical trial (NCT06724835) was conducted to evaluate its safety in patients with Nectin-4-positive advanced breast cancer. Although CT293 exhibited low toxicity risk preclinically, one patient developed on-target/off-tumor toxicities affecting the skin, oral mucosa, and gastrointestinal tract — indicating that systematic risk assessment is essential when developing such cell therapies.