Immune Cell Modulation of Patient-Matched Organoid Drug Response in Precision Cancer Medicine Platform.

Cancer is one of the leading causes of death worldwide, and the majority of cancer-related deaths are caused by cancer that has spread to other organs. Precision cancer medicine (PCM) holds potential to improve outcomes and relies on molecularly matched therapies based on cancer cell specific molecular alterations. The tumor immune microenvironment plays an important role beyond response to therapy; however, this is generally not considered in current PCM platforms. We established patient-matched organoids and immune cell cultures for drug testing in mono- and co-culture treatment setups using three distinct treatment strategies (pretreatment, co-culture treatment, and T-cell bispecific antibody testing). Response to treatment and impact of immune cells were evaluated by tumor cell viability assays and flow cytometry analysis. Phenotypic analysis showed high heterogeneity of tumor-infiltrating lymphocytes (TILs) across the patients and low immune cell portions of organoids, emphasizing the need for a patient-matched co-culture PCM approach. Our in-depth study of three patients revealed an effect of the patients' immune cells on drug response and T-cell bispecific antibody treatment in vitro. Here, we illustrate a state-of-the-art co-culture PCM pipeline for patient-matched organoids and immune cells replicating patient response to treatment at the time of biopsy.