Scale-up of breast and colorectal cancer organoids for high throughput screening

There is an urgent and unmet medical need to discover new cancer therapeutics that specifically target diseased cells and minimise adverse side-effects. One of the hurdles to be overcome in identifying new treatments is the availability of a lab-based test system that can accurately predict the efficacy of novel compounds for further clinical development.

The use of human-derived tumour organoids is revolutionising the preclinical testing of potential therapeutic compounds. They are a more advanced and biologically relevant model than flat, 2D cultures that are traditionally used in compound screening.

Organoids are 3D structures, that can be derived in the lab from normal and tumour tissue. A tiny, cancer biopsy sample for example, can be grown manually, in specialised laboratories, to form multiple copies, which are fully representative of the anatomy and disease pathology of the original tissue. When treated with drugs, the effect on cancer organoids, mirrors the patient response. Their increased selectivity and sensitivity to test compounds better predicts efficacy in the clinic, resulting in fewer false positives or negatives. This increases the quality of compounds that progress to later stages of development and decreases the likelihood that they will fail during toxicity testing or clinical trials - a particularly costly but common occurrence.

In order to produce organoids on a larger scale, for more widespread commercial use, Cellesce has developed a unique, patented bioprocess that can produce sufficient cancer organoids for research or small compound screens. The next stage is to scale-up organoid production further for use by pharmaceutical companies to find and select new anti-cancer drugs. For this purpose, a next-generation bioprocess is currently in the final stages of development. This will scale organoid production to 5 times the current capability, with the manufacture of more than 20 million organoids per batch; sufficient for high- throughput screens, early in the cancer drug-development pipeline. In additon, this improvement and scale-up will yield organoids that are cheaper, more reproducible and have lower batch-to-batch variation -- critical features for drug screening.

An Innovate UK loan would enable CSE to accelerate the pilot and full-scale testing of this innovative and unique bioprocess, for colorectal, breast, normal and cancer organoids. The output will be fully characterised to show maintenance of the same character as manually grown organoids. They will be validated with known therapeutics to demonstrate efficacy based on their underlying genetic susceptibility and used in a Proof-of-Concept drug screen.