Primary hypothesis: Drug screening of patient-derived organoids is a feasible method to identify effective and ineffective therapies for personalized colorectal cancer treatment.~Secondary hypothesis: Pre-treatment with cytotoxic agents can induce cellular immunotherapy efficacy against solid tumors in a colorectal cancer patient-derived organoid model.~Primary objective: To provide methodology and competencies for a clinical trial on drug screening on patient-derived organoids as an approach in personalized cancer treatment.~Secondary objective: To explore induction of cellular immunotherapy efficacy in colorectal cancer patient-derived organoids by chemotherapy or targeted agents.
In this study, the investigators will establish a reliable method and logistic pipeline for personalized drug testing ex vivo using fresh tumor samples from colorectal cancer (CRC) patients. With this, the investigators aim to develop a novel predictive biomarker of immunotherapy response, by testing combinations of chemotherapies and chimeric antigen receptor (CAR) T cells. Critically, this affects a large subgroup of patients currently not considered to benefit from such treatment. To support the hypothesis, the project will make use of cutting-edge, cell-based functional diagnostics. Individual patients' cancer cells will be screened against a panel of chemotherapies and targeted therapies including CAR T cells, to assess the optimal combination of therapies to induce immunotherapy efficacy in otherwise unresponsive CRC.