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SUMMARY:Single-cell spatial pharmacobiology identifies conserved stromal barriers to therapeutic antibody delivery in human solid tumors
DESCRIPTION:Statistical Bioinformatics SeminarSpeaker: Dr Guolan Lu\, Stanford University \n\n\n\nThis is an online event held via Zoom: https://uni-sydney.zoom.us/j/85114748391 \n\n\n\n\n\n\n\n\n\nThe development of effective antibody therapeutics has been hampered by a lack of methods to measure drug delivery and activity within tumors at single-cell resolution. Here we introduce single-cell spatial pharmacobiology (SSP)\, an experimental and 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 participants with head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma who received the antibody panitumumab-IRDye800 in phase 1 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-positive cancer-associated fibroblast neighborhoods\, which were associated with reduced antibody delivery in both tumor types. SSP measures drug–target–TME interactions in human tumors and can support studies of resistance mechanisms\, dosing strategies and discovery of spatial biomarkers for precision oncology. \n\n\n\n\n\n\nSubscribe to our seminar mailing list\n\n\n\n\n→\n\n\n\n\n\n\n\nFind out more about the Statistical Bioinformatics seminar series\n\n\n\n\n\n→\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nDr Guolan Lu\n\n\n\nGuolan Lu is a tenure-track Assistant Professor at Stanford University. Her laboratory develops spatial multi-omics and artificial intelligence technologies to determine how tissue organization shapes disease progression and therapeutic response. During her postdoctoral training at Stanford with Eben Rosenthal and Garry Nolan\, she designed and led a first-in-human fluorescence-guided surgery study in pancreatic cancer and pioneered single-cell spatial pharmacobiology in human tumors. She received her PhD through the joint Biomedical Engineering program at Georgia Tech and Emory University. \n\n\n\nConnect with Guolan:X: @GuolanLu
URL:https://spds.sydney.edu.au/event/single-cell-spatial-pharmacobiology-identifies-conserved-stromal-barriers-to-therapeutic-antibody-delivery-in-human-solid-tumors/
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