(1069-B) Enhancing Functional Precision Medicine by Utilizing Ex Vivo Drug Sensitivity Testing of Primary Patient Cells

Abstract: High Throughput Biomedicine (HTB) core laboratory has a long-standing history of offering assay ready compound plates and high throughput screening services for both academic as well as industrial partners nationally and internationally. This laboratory is a part of Institute for Molecular Medicine, Finland (FIMM). In collaboration with researchers and clinicians, we have established a Functional Precision Medicine program utilizing the Drug Sensitivity and Resistance Testing (DSRT) platform (Pemovska et al 2013). Our work has involved profiling the ex vivo responses of 715 primary cancer samples to an extensive collection of up to 528 clinical oncology and signal transduction inhibiting compounds (FIMM Oncology collection). The FIMM collections are regularly quality controlled by functional testing to ensure compound activity (Kulesskiy et al 2016), and updated regularly with the latest published anti-cancer molecules. Currently we have over 900 cancer related and other compounds that can be utilized for custom compound panels for screening.

We have screened mainly acute myeloid leukemia (AML) and multiple myeloma patient’s cells using DSRT assessing cell viability and toxicity. The clinical, molecular and functional data has been integrated by a Functional Precision Medicine Tumor Board (FPMTB) for application in clinical treatment decisions for AML patients. Actionable drugs have been found for 97% of relapsed or refractory AML patients (Malani et al 2022). Objective response rate was 59% for the individually tailored therapies including 13 complete responses. Additionally, we have developed and utilized flow cytometry-based screening methods for AML, myelodysplastic syndromes (MDS), acute lymphoblastic leukemia (ALL) and multiple myeloma samples to determine cell population based drug responses.

HTB laboratory is also a High Capacity Screening Partner Site in the EU-OPENSCREEN ERIC, hosting a collection of over 100,000 compounds, consisting of commercial substances and proprietary compounds from European chemists.

DSRT ex vivo drug testing serves as a powerful approach for understanding disease biology and drug sensitivity, facilitating the repositioning of known and emerging drugs for therapeutic purposes. HTB laboratory offers expertise and easy access for high throughput screening services, and for creating assay ready compound plates with flexible designs from single compound dose response to complex combinations.

References:
Pemovska et al. Individualized systems medicine strategy to tailor treatments for patients with chemorefractory acute myeloid leukemia. Cancer Discov. 2013 Dec;3(12):1416-29.

Kulesskiy et al. Precision Cancer Medicine in the Acoustic Dispensing Era: Ex Vivo Primary Cell Drug Sensitivity Testing. J Lab Autom. 2016 Feb;21(1):27-36.

Malani et al. Implementing a Functional Precision Medicine Tumor Board for Acute Myeloid Leukemia. Cancer Discov. 2022 Feb;12(2):388-401.