Patient-derived micro-organospheres (MOS) enable clinical precision oncology

Patient-derived xenografts (PDX) and organoids (PDO) 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 (MOS) from low-volume patient tissues, which serve as an ideal patient-derived model for clinical precision oncology. A clinical study of newly diagnosed metastatic colorectal cancer (CRC) patients using a MOS-based precision oncology pipeline reliably predicted patient treatment outcome within 14 days, a timeline suitable for guiding treatment decisions in clinic. Furthermore, MOS 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. Overall design: Using high-throughput sequencing technology (single cell sequencing and whole exon sequencing) to validate micro organospheres can keep the immune microenvironment and also keep genetic mutation status from patient derived tumor tissues.