Improved engineering and manufacture of iPSC-derived CAR-NK cells for immunotherapy

Cancer is still a leading cause of death worldwide, and is thought to have been responsible for 9.6million deaths in 2018 (about 1 in 6 deaths). Unfortunately, despite improvements in cancer care and treatment, the incidence and the number of deaths from cancer are set to increase along with an aging and growing population. There is therefore a need for more effective treatments.

Immunotherapy aims to boost the body's immune system to fight disease, and can be used to fight cancer. It uses substances made by the body or in a laboratory to improve how the body's immune system works to find and destroy cancer cells. Cellular immunotherapy is one type of immunotherapy that uses special blood cells of the immune system (T-cells or natural killer cells), and 'arms' them with the capacity to detect and destroy tumour cells.

These so-called 'chimeric antigen receptor (CAR)-T' or 'CAR-NK' cells have revolutionised the treatment of patients with otherwise incurable cancers.

However, these therapies have so far mostly relied on harvesting these blood cells from the patient or healthy donors. Whilst this method does work, it makes this therapeutic approach unpredictable, very expensive, and it requires a complex infrastructure for delivery. Another problem has been the development of adverse side effects in some patients with the use of CAR-T cell therapies.

Therefore, any therapy that seeks to reduce variability, decrease cost, increase safety and make the manufacturing process faster and/or more robust, is hugely attractive. One such area of research is the use of 'induced pluripotent stem cells' (iPSCs). These cells can be made from adult tissue, and have the capacity to be cultured in the lab indefinitely and, more importantly, to give rise to any type of cell in the body - making them an ideal starting material for the manufacture of off-the-shelf cell therapies.

They are also very amenable to genetic modification, which also makes them ideal for the 'arming' process mentioned above.

There are two major aims of this project. The first is to deploy LambdaGen's advanced gene editing technology to arm iPSCs with multiple elements for enhanced capabilities for the detection and killing of tumour cells. The second is to deploy Plasticell's next generation screening technology to develop efficient methods to generate iPSC-derived natural killer cells. The combination of these two technologies promises to create an affordable, effective and safe therapy for the treatment of cancer.