Base edited T cell therapy against T-ALL (TvT)

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Over the past few years it's become possible to use a patient's own immune cells to fight certain types of blood cancer. Generally, white blood cells called T cells are collected and taken to a special clean room, where they are modified using a disabled virus. This adds extra DNA code that programs he cells to fight leukaemia. We have previously shown that it's possible to use additional steps to allow T cells to be used from donors without any matching. These steps originally used molecular scissors called TALENs, and in 2015 we successfully treated two infants in the UK and then started clinical trials in children and adults, which were recently published. At GOS, we are now using a next version of the strategy after making ready-made CAR T cells using new versions of the scissors called CRISPR to snip two genes in T cells that allow them to used without matching. In this new application, we want to extend the approach to used donor T cells other blood cancers, including T cell leukaemia. Up to now, this hasn't been possible because T cells armed to fight other T cells have been difficult to grow because they end up fighting each other. In recent experiments we have used genome-editing to remove markings on T cells so they become invisible and are not targeted during the engineering steps. Rather than cutting DNA, we have used an even newer version of CRISPR that changes a single letter (or base) to tell cells to stop showing their markings, also to allow them to be used without matching. A clinical trial is proposed to treat 10 children from a cross the UK over a two year period, as part of planned bone marrow transplantation (BMT). If T cells can be used to eliminate measurable leukaemia, the chances of it coming back after BMT are very much reduced. Careful tracking of side effects and anti-cancer activity will be provided, especially in the first 4 weeks after treatment, but will continue for a year to make sure the treatment is both safe and effective.