TY - JOUR KW - Colonic Neoplasms KW - Humans KW - Immunotherapy KW - organoids KW - Precision Medicine KW - adoptive cell therapy KW - bispecific antibody KW - colorectal cancer KW - droplet microfluidics KW - immune-oncology KW - lung cancer KW - micro-organosphere KW - Precision Medicine KW - precision oncology KW - tumorsphere AU - Shengli Ding AU - Carolyn Hsu AU - Zhaohui Wang AU - Naveen R. Natesh AU - Rosemary Millen AU - Marcos Negrete AU - Nicholas Giroux AU - Grecia O. Rivera AU - Anders Dohlman AU - Shree Bose AU - Tomer Rotstein AU - Kassandra Spiller AU - Athena Yeung AU - Zhiguo Sun AU - Chongming Jiang AU - Rui Xi AU - Benjamin Wilkin AU - Peggy M. Randon AU - Ian Williamson AU - Daniel A. Nelson AU - Daniel Delubac AU - Sehwa Oh AU - Gabrielle Rupprecht AU - James Isaacs AU - Jingquan Jia AU - Chao Chen AU - John Paul Shen AU - Scott Kopetz AU - Shannon McCall AU - Amber Smith AU - Nikolche Gjorevski AU - Antje-Christine Walz AU - Scott Antonia AU - Estelle Marrer-Berger AU - Hans Clevers AU - David Hsu AU - Xiling Shen AB - 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. BT - Cell Stem Cell DA - 2022-06-02 DO - 10.1016/j.stem.2022.04.006 IS - 6 LA - eng N2 - 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. PY - 2022 SP - 905 EP - 917.e6 T2 - Cell Stem Cell TI - Patient-derived micro-organospheres enable clinical precision oncology VL - 29 SN - 1875-9777 ER -