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CAR-T therapy represents a breakthrough technology that has already been demonstrated to successfully treat cancer in Leukaemia and achieve specific clearance of tumour cells throughout the body. However, the current process removes patients own cells to alter them before returning them to the body. Treatments can therefore cost upwards of $400,000, take a month to be created and for now only work in less than 4% of liquid tumours. Given that the immune system is responsive and capable of manufacturing its own cellular defences, we wanted to understand why these altered cells could not be manufactured in the body itself. How might we manufacture CAR-T immunotherapies directly in the body?

The key obstacle was to alter the body’s immune cells without triggering an immune response and the ability to specifically target to T cells whilst being easy to manufacture. Nanoparticles appeared to be one delivery modality without these side effects. How might we deploy nanoparticles to re-engineer the body’s own defence systems against cancer? Even if you are able to alter cells without side effects, achieving stable expression for long enough for the treatment to be effective is challenging. Reframed opportunity: How might we create an injectable, specific gene therapy agent, that allows CAR-T cells to grow in vivo with stable expression?



By delivering CARs to T-cells in vivo, ITT’s technology eliminates the costly and complex cell bio- manufacturing process, replacing it with an injection of a freeze-dried, off-the-shelf product. T-cells transfected in vivo have now been shown to perform as well as state- of-the-art ex vivo transduced CARs. This will be effective not just in cancer, but also in infectious diseases such as HIV and autoimmune conditions such as rheumatoid arthritis.