Patient-derived micro-organospheres enable clinical precision oncology

Shengli Ding, Carolyn Hsu, Zhaohui Wang, Naveen R. Natesh, Rosemary Millen, Marcos Negrete, Nicholas Giroux, Grecia O. Rivera, Anders Dohlman, Shree Bose, Tomer Rotstein, Kassandra Spiller, Athena Yeung, Zhiguo Sun, Chongming Jiang, Rui Xi, Benjamin Wilkin, Peggy M. Randon, Ian Williamson, Daniel A. NelsonDaniel Delubac, Sehwa Oh, Gabrielle Rupprecht, James Isaacs, Jingquan Jia, Chao Chen, John Paul Shen, Scott Kopetz, Shannon McCall, Amber Smith, Nikolche Gjorevski, Antje Christine Walz, Scott Antonia, Estelle Marrer-Berger, Hans Clevers, David Hsu, Xiling Shen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

8 Citaten (Scopus)

Samenvatting

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 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.

Originele taal-2Engels
Pagina's (van-tot)905-917.e6
TijdschriftCell Stem Cell
Volume29
Nummer van het tijdschrift6
DOI's
StatusGepubliceerd - 2 jun. 2022

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