Abstract 5781: Establishment of a 3D ex-vivo assay as a preclinical drug testing platform for personalized cancer therapy

In vitro cell based drug testing tools have been widely used in drug discovery and early development to evaluate novel drug entities for further evaluation in preclinical in vivo models. However, a poor correspondence with in vivo models has compelled oncologists to pursue complementary in vitro strategies with better outcomes. Within this realm, a 3D ex vivo platform is being extensively used to evaluate the activity of cytotoxic drugs, targeted molecules, and antibodies. To increase the translational value of this model, maintenance of the tumor microenvironment (immune and other stromal cells) is highly pertinent. We have established a 3D ex vivo assay as a patient drug testing platform for personalized medicine therapies in collaboration with our clinical partners. In this study we setup the protocols for obtaining single cell suspensions from biopsy and/or tumor resection samples from patients presenting with Urothelial cancers, Renal cell carcinoma, Pancreatic, NSCLC, Ovarian, and Melanomas to generate 3D microtumors in 96 well format cultured over a period of 7-15 days. The microtumors were monitored for growth characteristics, biomarker phenotype and drug activity profile. As expected the growth characteristics for each tumor varied, corresponding very well with clinical disease progression. Subsequently, these microtumors were assessed using a standard clinical immunohistochemistry diagnostics approach to evaluate disease specific biomarkers and were compared to the clinical diagnostics profile of the patients. The biomarker profile from 3D derived tumor samples showed concordance with the patient diagnostics profile. In the instances were clinical information and treatment regimens were available, the microtumors were tested and followed with single and pairwise drug treatments. The ex vivo 3D treatment outcome clearly reflected the clinical outcome. Currently, this platform is being used to develop 3D ex vivo immune-competent models to study immunomodulatory therapies. Based on the overall data we conclude that the 3D ex vivo assay system offers a highly pertinent platform to perform chemosensitivity testing providing predictive information on the clinical outcome, which enables oncologists to redefine individualized chemo/targeted treatments. Citation Format: Sumeer Dhar, Francesca Chiovaro, Tamara Tanos, Tomas Hejhal, Seife Heilemariam, Jens Kelm, Anja Irmisch, Mitchell Levesque. Establishment of a 3D ex-vivo assay as a preclinical drug testing platform for personalized cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5781. doi:10.1158/1538-7445.AM2017-5781