3D in vitro system for measuring treatment responses to immunotherapy in CRC patients.

Abstract

e15114 Background: Current clinical guidelines for the treatment of cancer patients mainly rely on intrinsic characteristics of a given tumor, such as its localization, its staging and in some instances also known genetic markers. The success of treatment administered according to this proceeding is, however, undermined by large inter-individual variability of tumors. Embedded in a unique meshwork of extracellular matrix, stromal cell and bioactive factors, malignant cells accumulate a distinctive pattern of genetic, epigenetic and metabolic alterations, resulting in unrestricted growth. Despite the potential availability of tailored drugs, matching cancer drug therapy to the unique characteristics of a patient’s tumor, is generally unfeasible in clinical practice. Methods: Addressing this need, 2cureX developed a functional test (IndiTreat) for measuring the responsiveness of micro-tumors (tumoroids) derived from colorectal cancer (CRC) and liver metastases to chemotherapeutic agents, targeted therapies and combinations thereof. To further broaden the applicability of the IndiTreat test, the present study aims to adapt the assay system to functional testing of immunotherapeutics. The success of immunotherapeutic treatment (I/O) regimens is currently limited to a small subset of CRC patients such as those with microsatellite instability (MSI) high tumors. However, new chemo-immunotherapies may prove beneficial for a greater percentage of patients. Results: To pre-therapeutically assess the potential efficacy of I/O interventions for individual patients, we co-culture tumoroids and autologous PBMCs and monitor immune-mediated killing of tumoroids in vitro. Subsequently, these culture systems will be tested regarding their susceptibility towards an array of single or combined I/O drugs. Tumoroids recapitulate the highly individual disease of cancer patients and, as demonstrated by our allogenic setting, constitute a valuable platform for testing different aspects of immune-mediated tumor cell recognition and killing. Conclusions: In light of an increasing number of cost-intensive I/O treatment options becoming available to CRC patients, pre-therapeutic testing of individual responses to immunotherapy will be of key relevance in assisting the oncologist to select the most potent treatment regime for every patient available.