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Author Spotlight: Recreating Melanoma Complexity with Patient-Derived Organoids for Immunotherapy Evaluation
Published on: September 6, 2024
Patient-derived micro-organospheres enable clinical precision oncology
Shengli Ding1, Carolyn Hsu2, Zhaohui Wang1
1Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Xilis, Inc., Durham, NC 27713, USA.
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.
Insights
Rapidly generated micro-organospheres (MOSs) from patient tumors accurately predict cancer drug response within 14 days. This breakthrough enables timely clinical decisions and testing of novel immuno-oncology therapies.
Area of Science:
- Oncology
- Biotechnology
- Microfluidics
Background:
- Patient-derived xenografts (PDXs) and organoids (PDOs) model cancer therapy response but have limitations for timely clinical decisions.
- Current models struggle to provide rapid, actionable insights for precision oncology.
Purpose of the Study:
- To develop a rapid, patient-derived model for precision oncology.
- To assess the feasibility of using micro-organospheres (MOSs) to guide clinical treatment decisions.
- To evaluate MOSs as a platform for testing immuno-oncology (IO) therapies.
Main Methods:
- Utilized droplet emulsion microfluidics for rapid generation of thousands of micro-organospheres (MOSs) from low-volume patient tissues.
- Implemented temperature control and dead-volume minimization in the microfluidic system.
- Conducted a clinical study with metastatic colorectal cancer (CRC) patients to assess drug response using the MOS pipeline.
Main Results:
- MOSs were rapidly generated from patient tissues, serving as an ideal model for precision oncology.
- The MOS-based pipeline reliably assessed tumor drug response within 14 days for metastatic colorectal cancer (CRC) patients.
- MOSs successfully captured stromal cells and allowed T cell penetration, enabling testing of immuno-oncology (IO) therapies.
Conclusions:
- Micro-organospheres (MOSs) offer a rapid and effective patient-derived model for clinical precision oncology.
- The MOS platform provides a clinically relevant timeline for guiding cancer treatment decisions.
- MOSs are a valuable tool for evaluating the efficacy of immuno-oncology (IO) therapies, including PD-1 blockade and T cell therapies.
