Journal Article

DKFZ-2026-01366

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Single-cell spatial pharmacobiology identifies conserved stromal barriers to therapeutic antibody delivery in human solid tumors.

Lu, G. ; Hickey, J. W. ; Haist, M. ; Qin, X. ; Zhao, E. ; Naveed, A. ; Forgo, E. ; Baertsch, M.-A.DKFZ* ; Mani, L. ; Rovira-Clavé, X. ; Finegersh, A. ; Goltsev, Y. ; Caraccio, C. ; van den Berg, N. S. ; Hom, M. ; Colburg, D. R. ; Martin, B. A. ; Kong, C. S. ; Lui, N. S. ; Fisher, G. A. ; Colevas, A. D. ; West, R. B. ; Thurber, G. M. ; Poultsides, G. A. ; Nolan, G. P. ; Rosenthal, E. L.

2026
Springer Nature New York, NY

Abstract: The 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.

Note: epub

---

Contributing Institute(s):

1. KKE Mol. Hämatologie/Onkologie (A360)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---