Adoptive T cell immunotherapy therapy for adenovirus infection in transplant patients

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Bone marrow transplantation is used to treat leukaemia and involves the transfer of blood or bone marrow from a donor to the patient. Unfortunately patients have to be immunosuppressed to ensure that the graft is not rejected and this allows viruses that normally cause only mild symptoms to become a major threat to health. There are antiviral drugs available to treat some of these viruses (eg Epstein Barr Virus or cytomegalovirus) but for adenovirus there is no effective and approved treatment. Adenovirus normally causes mild respiratory infections in young children and most people have had at least one adenovirus infection by adolescence. As such we normally have a long lasting immunity to further infections with the same virus strain. We know that in the transplant setting, if the immune response to the virus can be restored, the patient has a good chance of controlling the infection. One way to do this is to use white (T) cells from the transplant donor, selecting just those cells that can recognise the virus, thereby halting the infectious cycle. This proposal aims to select adenovirus-specific T cells from the donor by binding them to a molecule that mimics the part of the virus that they would normally recognise. This molecule is itself tagged to a microscopic magnetic particle so that the required cells can be separated from other cells and transplanted into the bone marrow recipient. This work has proven safe and effective in situations in which the donor has a large immune response to the virus but now we wish to develop it in a more challenging situation in which the level of the immune response is much smaller. The research will be conducted as an early phase clinical trial which aims to establish the feasibility of the method but will also have the secondary objective of minimising the adenovirus infection.