Development of an integrated and scalable platform process for the robust manufacture of allogeneic iPSC immunotherapies

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Modern therapies are often concerned with using human cells as therapeutic modalities. Recent breakthroughs in the treatment of leaukemia and lymphoma are associated with the administration of patient's own isolated T-lymphocyes, modified at the laboratory to recognise and kill tumour cells. However, such therapies have strong side effects, require time for producing the cells for treatment and are not always afforadable due to high costs. A new approach in immuno-oncology is to utilize another type of lymphocytes -- Natural killer (NK) cells. These cells can become active and efficiently eliminate cancer cells, including solid tumours, with minimal side effects. Importantly, they can be obtained from the peripheral or cord blood with no strict requirements for the matching donor. The next generation therapy originates from the production of NK cells from the human induced pluripotant stem cells (iPSC) as a universal off-the-shelf product. Such technology not only allows to create an unlimited source of the therapeutic agents, but to target the produced NK cells to a specific cancer cell type in a patient-centered approach by genetically modifying the starting iPSC material.In the proposed collaboration, Plasticell, Cell and Gene therapy Catapult and Imperial College London aim to develop a manufacturing procedure for iPSC-derived fully functioning NK cells for immuno-therapies. Plasticell has deployed its award-winning screening platform to generate protocols for differentiation of NK cells from iPSCs. This technology will be transferred to the Cell and Gene therapy Catapult to be adapted to a manufacturing scale. Finally, all assays to test the functionality of produced NK cells will be developed under control and guidance of the NK cell specialist Prof Hugh Brady at Imperial Colledge London. We aim at developing a process of a robust and efficient production of human NK cells in conditions that can be easily translated to the clinical practice. Throughout the project, all the materials and methods used will be clinically acceptable with the purpose to generate functionally mature NK cells in high yield and purity. The produced NK cells will be tested for their compatibility with donor-derived NK cells and their ability to kill cancer cells in the laboratory settings. The success of this project will lead to comprehensive pre-clinical studies using advanced research techniques and animal-based cancer models, and developing next generation therapies for solid tumours.