Novel antibody drug candidates and innovative screening tools to target cancer stem cells

Over the years, extensive research has led to a number of treatment strategies against cancer. However, cancer cells evolve and develop mechanisms to resist or escape most treatments. The theory that cancer onset, maintenance and progression is due to a small population of cancer stem cells (CSCs) is gaining ground.

New strategies need to be designed to target CSCs. The EU-funded SUPPRESSTEM (Testing and validation of bispecific antibody combinations targeting treatment-resistant cancer stem cells using organoid-based screening tools: a new drug discovery paradigm) project is developing novel bispecific antibody-based therapeutics to treat colorectal cancer. These are designed to target CSC-specific developmental, growth and survival pathways such as the Wnt signalling pathway with minimal toxicity on healthy tissue.

To maximise the clinical efficiency of the SUPPRESSTEM drug candidates, researchers are directly screening relevant human patient material using organoids and novel imaging technologies. During the first part of the project, researchers generated over 500 different bispecific antibodies against six different CSC targets that were tested on colon cancer organoids. Currently they are using these antibodies to identify suitable drug candidates. In parallel a high throughput screening assay based on patient derived colon cancer organoids was successfully developed and validated using imaging as readout.

The organoid cultures could be potentially isolated from each patient. The SUPPRESSTEM in vitro system could thus be used to personalise and predict treatment response. In the long term, this will minimise unnecessary suffering from drug side effects and improve patient survival and quality of life.