3D ex-vivo assay platform using primary cancer cells in malignant pleural effusions as predictor for clinical outcome of personalized chemotherapy
Cheng-guang Wu1, Francesca Chiovaro2, Alessandra Curioni3, Sumeer Dhar2, Alex Soltermann1
- Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
- InSphero, Schlieren, Switzerland
- Department of Oncology, University Hospital Zurich, Zurich, Switzerland.
Background It has been observed that patients suffering from same cancer type may respond very differently to a given chemotherapeutic regimen. We propose the development of a unique patient-derived 3D ex-vivo drug testing platform which may offer greater prediction of clinical outcomes and may present a valid decision making tool to propose 2nd or 3rd line treatment regimens.
Methods In this ex-vivo platform freshly collected malignant pleural effusions from patients were prepared for a 96 well based 3D ex-vivo assay format using the hanging drop method and a parallel 2D cell culture format. Subsequently, we compared the original cell composition of the malignant effusion with respective micro-tumours generated in the 3D format. Micro-tumours were fixed, embedded in paraffin and processed like original cell blocks.
Results Our ex-vivo 3D platform could efficiently generate microtumors out of malignant pleural effusions. This 3D platform could potentially keep the diagnostic marker expression of cancer cells as well as maintain the cell proliferation for different cancer types. Moreover, original immune cells were quenched out during culture.
Conclusion Our model presents an optimal condition to conduct chemosensitivity/-resistance profiling in individual cancer patients in the future.