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13 March 2024 Direct measurement trials: use of optically labeled therapeutic antibodies in human trials identifies novel barriers to delivery in intact human tumors
Eben L. Rosenthal M.D., Guolan Lu, Gary Nolan
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Proceedings Volume PC12821, Visualizing and Quantifying Drug Distribution in Tissue VIII; PC1282103 (2024) https://doi.org/10.1117/12.3009461
Event: SPIE BiOS, 2024, San Francisco, California, United States
Abstract
The effectiveness of antibody therapeutics relies on in vivo drug pharmacology, intrinsic parameters of tumor cells, and tumor microenvironment factors. An understanding of the antibody-target-microenvironment interactions will improve patient selection and development of new targeted therapeutics. Using optically labeled therapeutic antibodies systemically delivered to patients prior to surgical resection, we were able to develop a novel analytical method to measure therapeutic behavior of these agents and their cellular targets at single cell resolution within intact human tumors. We identified two major subtypes of CAFs as well a unique enrichment of extracellular matrix components with the tumor. The spatial arrangement of ECM proteins were also associated with reduced therapeutic antibody penetration. Our findings were further supported by spatial transcriptomics of adjacent tissue slices and public scRNA seq data. This study provides a new framework for interrogating drug pharmacology in conjunction with tumor biology, opening new avenues for dosing optimization, biomarker identification, and the development of new stromal-targeting therapies to improve treatment outcomes.
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Eben L. Rosenthal M.D., Guolan Lu, and Gary Nolan "Direct measurement trials: use of optically labeled therapeutic antibodies in human trials identifies novel barriers to delivery in intact human tumors", Proc. SPIE PC12821, Visualizing and Quantifying Drug Distribution in Tissue VIII, PC1282103 (13 March 2024); https://doi.org/10.1117/12.3009461
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KEYWORDS
Tumors
Therapeutic antibodies
Pharmacology
In vivo imaging
Matrices
Proteins
Resection
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