Patient-derived micro-organospheres enable clinical precision oncology
Ding, Shengli; Hsu, Carolyn; Wang, Zhaohui; Natesh, Naveen R.; Millen, Rosemary; Negrete, Marcos; Giroux, Nicholas; Rivera, Grecia O.; Dohlman, Anders; Bose, Shree; Rotstein, Tomer; Spiller, Kassandra; Yeung, Athena; Sun, Zhiguo; Jiang, Chongming; Xi, Rui; Wilkin, Benjamin; Randon, Peggy M.; Williamson, Ian; Nelson, Daniel A.; Delubac, Daniel; Oh, Sehwa; Rupprecht, Gabrielle; Isaacs, James; Jia, Jingquan; Chen, Chao; Shen, John Paul; Kopetz, Scott; McCall, Shannon; Smith, Amber; Gjorevski, Nikolche; Walz, Antje Christine; Antonia, Scott; Marrer-Berger, Estelle; Clevers, Hans; Hsu, David; Shen, Xiling
(2022) Cell stem cell, volume 29, issue 6, pp. 905 - 917.e6
(Article)
Abstract
Patient-derived xenografts (PDXs) and patient-derived organoids (PDOs) have been shown to model clinical response to cancer therapy. However, it remains challenging to use these models to guide timely clinical decisions for cancer patients. Here, we used droplet emulsion microfluidics with temperature control and dead-volume minimization to rapidly generate thousands of
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micro-organospheres (MOSs) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of recently diagnosed metastatic colorectal cancer (CRC) patients using an MOS-based precision oncology pipeline reliably assessed tumor drug response within 14 days, a timeline suitable for guiding treatment decisions in the clinic. Furthermore, MOSs capture original stromal cells and allow T cell penetration, providing a clinical assay for testing immuno-oncology (IO) therapies such as PD-1 blockade, bispecific antibodies, and T cell therapies on patient tumors.
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Keywords: adoptive cell therapy, bispecific antibody, colorectal cancer, droplet microfluidics, immune-oncology, lung cancer, micro-organosphere, precision medicine, precision oncology, tumorsphere, Molecular Medicine, Genetics, Cell Biology
ISSN: 1934-5909
Publisher: Cell Press
Note: Funding Information: The authors acknowledge funding from National Institutes of Health, United States ( NIH) U01 CA217514 and U01 CA214300 and the Duke Woo Center for Big Data and Precision Health . Funding Information: The authors acknowledge funding from National Institutes of Health, United States (NIH) U01 CA217514 and U01 CA214300 and the Duke Woo Center for Big Data and Precision Health. Conceptualization, N.G. A.-C.W. S.A. E.M.-B. H.C. D.H. and X.S.; methodology, S.D. Z.W. A.S. D.H. and X.S.; formal analysis, S.D. C.H. Z.W. and N.R.N.; investigation, S.D. C.H. Z.W. M.N. G.O.R. T.R. K.S. R.X. B.W. P.M.R. A.Y. Z.S. I.W. D.A.N. D.D. and S.O.; formal analysis, A.D. C.J. C.C. and N.G.; resources, R.M. J.J. J.I. A.S. G.R. S.M. N.G. A.-C.W. E.M.-B. J.P.S. P.M.R. B.W. and S.K.; data curation, S.D. and N.G.; writing – original draft, S.D. S.B. N.G. A.D. D.H. and X.S.; writing – review & editing, Z.W. C.H. H.C. N.R.N. R.M. J.I. D.H. and X.S.; visualization, S.D. and X.S.; supervision, H.C. D.H. and X.S.; project administration, S.D.; funding acquisition, D.H. and X.S. X.S. D.H. and H.C. are cofounders of Xilis Inc. H.C. is an employee of Roche and on the advisory board of Cell Stem Cell. H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers/. S.D. and Z.W. performed the majority of the study at Duke University and now are employees of Xilis Inc. Patents WO2020242594 and US 2021/0285054 are related to this work. Publisher Copyright: © 2022 Elsevier Inc.
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