An important part of our work in this theme relates to the modification or editing of T cells. T cells are white blood cells that are an important part of the body’s immune system. They detect and destroy abnormal cells, such as cancer cells. If your T-cells don’t work properly, abnormal cells can grow and multiply.
T cell receptor gene therapy for blood cancers
This research is finding ways to use T cells to create treatments for blood cancer.
Teams led by Professors Ronjon Chakraverty and Paresh Vyas have found a way to identify T cell receptors (TCRs) that react to blood cancer cells.
TCRs join onto particular proteins that can be found on the surface of blood cancer cell surface. This prompts the immune system to fight against that cell.
If we can make T-cells that ‘switch on’ these TCRs, then the cells can be used as a treatment for several different kinds of blood cancer. Unlike other T-cell therapies, these treatments would not need to be manufactured to match the cells of each individual patient: they would work for lots of different people, known as an ‘off-the-shelf’ therapy.
In partnership with Oxford Biomedica we are designing a way to test how T cells might switch on TCRs in the correct way. We hope that this work will lead to clinical trials to test these TCRs in patients for the first time.
Gene editing of T cells to treat multiple sclerosis
Some of our research is finding out how to edit genes to provide protection against disease.
From looking at information about the genomes of multiple people, a team led by Dr Calliope Dendrou has been able to identify a variant of a normal gene that protects against autoimmune diseases such as multiple sclerosis (MS). This is a variant in the TYK2 gene.
Professor Adam Wilkinson and Professor James Davies are researching how we can edit the TYK2 gene in blood stem cells to make sure it includes this protective variant. The stem cells could then be given as a transplant into people with MS, and hopefully slow the disease or stop it getting worse.
We are working with the NIHR Sheffield BRC to obtain clinical samples from MS patients to test whether or not this gene editing approach works. We will work with MS patient groups and carry out an early phase trial in people with ‘high risk’ MS.