Establishment of ex vivo drug sensitivity screening platform for leukaemia and multiple myeloma using a south african patient cohort

Our objective is to develop a functional precision medicine platform designed to directly identify tailored drug regimens that target individual patient cancer cells and give benefit to the same donors by supporting clinical decision-making. We demonstrate our ex vivo drug sensitivity screening platform for precision medicine using Leukaemia and Multiple Myeloma samples from a South African patient cohort as proof of concept. Through collaboration with Chris Hani Baragwanath and Donald Gordon Hospitals, Johannesburg, South Africa, we performed patient sample collections of n=80. Collected patient samples include Acute myeloid leukaemia (AML) (n=7), Chronic lymphocytic leukaemia (CLL) (n=4), Chronic myeloid leukaemia (CML) (n= 30), Multiple Myeloma (n=40) and health donor (n=5). For each patient sample, peripheral blood mononuclear cell (PBMC) isolation was performed and cryopreseved in liquid nitrogen. Our preliminary demographic analysis results show that we can group patients based on diagnosis, staging, exclusion and inclusion criteria. From our demographic analysis, we have also identified highly frequent chemotherapy drugs used in the cohort. Further, we can identify the most frequent chemotherapy drugs given as medication to the patient cohort. We then selected 30 drugs that are relevant for leukemia and multiple myeloma for Ex vivo drug sensitivity screening test. Using our results we will then select effective drugs for monotherapy and also drug combinations. Selected drug combinations will then be validated on patient samples using our ex vivo drug sensitivity test. These results will be analyzed using our statistical capabilities and developed as a packaged product of preclinical information for precision clinical trials. Thus, we are progressing our cutting-edge translational platform from technology readiness level (TRL4) to TRL6 on blood cancer.