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 Nelson; Daniel 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

doi:10.1016/j.stem.2022.04.006

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

66 Citations (Scopus)

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 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.

Original language	English
Pages (from-to)	905-917.e6
Journal	Cell Stem Cell
Volume	29
Issue number	6
DOIs	https://doi.org/10.1016/j.stem.2022.04.006
Publication status	Published - 02 Jun 2022

Keywords

Colonic Neoplasms/pathology
Humans
Immunotherapy
Organoids/pathology
Precision Medicine

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10.1016/j.stem.2022.04.006

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Ding, S., Hsu, C., Wang, Z., Natesh, N. R., Millen, R., Negrete, M., Giroux, N., Rivera, G. O., Dohlman, A., Bose, S., Rotstein, T., Spiller, K., Yeung, A., Sun, Z., Jiang, C., Xi, R., Wilkin, B., Randon, P. M., Williamson, I., ... Shen, X. (2022). Patient-derived micro-organospheres enable clinical precision oncology. Cell Stem Cell, 29(6), 905-917.e6. https://doi.org/10.1016/j.stem.2022.04.006

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title = "Patient-derived micro-organospheres enable clinical precision oncology",

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 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.",

keywords = "Colonic Neoplasms/pathology, Humans, Immunotherapy, Organoids/pathology, Precision Medicine",

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

year = "2022",

month = jun,

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doi = "10.1016/j.stem.2022.04.006",

language = "English",

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Ding, S, Hsu, C, Wang, Z, Natesh, NR, Millen, R, Negrete, M, Giroux, N, Rivera, GO, Dohlman, A, Bose, S, Rotstein, T, Spiller, K, Yeung, A, Sun, Z, Jiang, C, Xi, R, Wilkin, B, Randon, PM, Williamson, I, Nelson, DA, Delubac, D, Oh, S, Rupprecht, G, Isaacs, J, Jia, J, Chen, C, Shen, JP, Kopetz, S, McCall, S, Smith, A, Gjorevski, N, Walz, A-C, Antonia, S, Marrer-Berger, E, Clevers, H, Hsu, D & Shen, X 2022, 'Patient-derived micro-organospheres enable clinical precision oncology', Cell Stem Cell, vol. 29, no. 6, pp. 905-917.e6. https://doi.org/10.1016/j.stem.2022.04.006

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AU - Hsu, Carolyn

AU - Wang, Zhaohui

AU - Natesh, Naveen R

AU - Millen, Rosemary

AU - Negrete, Marcos

AU - Giroux, Nicholas

AU - Rivera, Grecia O

AU - Dohlman, Anders

AU - Bose, Shree

AU - Rotstein, Tomer

AU - Spiller, Kassandra

AU - Yeung, Athena

AU - Sun, Zhiguo

AU - Jiang, Chongming

AU - Xi, Rui

AU - Wilkin, Benjamin

AU - Randon, Peggy M

AU - Williamson, Ian

AU - Nelson, Daniel A

AU - Delubac, Daniel

AU - Oh, Sehwa

AU - Rupprecht, Gabrielle

AU - Isaacs, James

AU - Jia, Jingquan

AU - Chen, Chao

AU - Shen, John Paul

AU - Kopetz, Scott

AU - McCall, Shannon

AU - Smith, Amber

AU - Gjorevski, Nikolche

AU - Walz, Antje-Christine

AU - Antonia, Scott

AU - Marrer-Berger, Estelle

AU - Clevers, Hans

AU - Hsu, David

AU - Shen, Xiling

PY - 2022/6/2

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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.

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.

KW - Colonic Neoplasms/pathology

KW - Humans

KW - Immunotherapy

KW - Organoids/pathology

KW - Precision Medicine

U2 - 10.1016/j.stem.2022.04.006

DO - 10.1016/j.stem.2022.04.006

M3 - Article

C2 - 35508177

SN - 1934-5909

VL - 29

SP - 905-917.e6

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 6

ER -

Patient-derived micro-organospheres enable clinical precision oncology

Abstract

Keywords

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