Pharmacoscopy – Watching drug action under the microscope.
Once reserved for adherent cell lines, a new and powerful technology, which we termed Pharmacoscopy, allows the quantification of single-cell events in a high-throughput and high-content manner.
Members of the Superti-Furga lab, in collaboration with the Department of Hematology of the Medical University of Vienna, developed Pharmacoscopy to screen liquid primary patient material using automated confocal microscopy. It allows the quantification of single-cell events such as differential cell death, protein expression, cell morphology and more over many perturbations – creating robust and unique data sets. Further, the single-cell-to-global resolution enables the mapping of cell-cell contacts, enabling the study of immune and cancer-immuno events like never before.
Differential drug specificities and personalized medicine
The technology has enabled us, with our partner hemato-oncologists, to determine the best treatment for patients with late stage and refractory hematological malignancies. With Pharmacoscopy, investigation is under way into the clinical translation of differential cytotoxicity, meaning the death of cancer cells versus healthy cells, and how this relates to patient outcome on a particular drug. This work is in review (Snijder et al), can be found on clinicaltrial.gov (NCT03096821), and is supported with ERC proof of concept and WWTF life science grants.
Enabling the discovery of immunomodulatory therapies
Further, the use of immunomodulatory drugs has rapidly changed the way we think about harnessing the immune system to control cancer in patients: the goal is to modulate the physical proximity of cancer cells to cell death inducing effector cells such as NK- and T-cells. However, as of recently, there had been no robust methods to screen for drugs of biologics that specifically induce these necessary cell-cell contacts.
Pharmacoscopy can, in very high-throughput, quantify the physical distance of cell-types of interest, enabling such screening. We used this system to classify a library of drugs for their immunomodulatory effect, and worked to uncover a new mechanism of one such drug. This study can be found in our recent publication in Nature Chemical Biology (Vladimer et al, 2017), and was outlined very well by Derek Lowe in a post on Science Translational Medicine titled “Silently Affecting the Immune System?”
We believe that Pharmacoscopy has huge potential not only in cancer and immunology research, but can also be applied for a large variety of other diseases and model systems.