Single-cell spatial pharmacobiology identifies conserved stromal barriers to therapeutic antibody delivery in human solid tumors

Here we introduce single-cell spatial pharmacobiology (SSP), an analytical framework that integrates in situ imaging of a systemically infused, fluorescently labeled therapeutic antibody with high-plex spatial proteomics to quantify antibody distribution, target engagement, and tumor microenvironment (TME) architecture.

We applied SSP to tumor tissues from patients with head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma who had received the antibody panitumumab-IRDye800 in phase I trials. SSP identified pronounced spatial heterogeneity in single-cell drug delivery and target engagement, shaped by conserved stromal barriers, including periostin-rich extracellular matrix assemblies and fibroblast activation protein⁺ cancer-associated fibroblast neighborhoods, which were associated with reduced antibody delivery in both tumor types.