Next generation T-cell therapies for CMV post-allogeneic stem cell transplant

Cytomegalovirus (CMV) affects 50-80% of UK adults and is of limited significance in healthy individuals. However, following stem-cell-transplantation (allo-SCT), CMV can be life-threatening. Despite advances, drug treatments are unsatisfactory due to severe toxicities, viral resistance, high costs and prolonged hospitalisation. An alternative approach is to harness the immune-system to target CMV. Clinical trials of CMV T-cell immunotherapies in allo-SCT patients appear to control CMV with minimal side-effects. Allo-SCT patients at highest risk for CMV are those with graft-versus-host-disease (GvHD), a devastating condition requiring treatment with immune-suppressing drugs including glucocorticoids. Glucocorticoids improve GvHD, but kill CMV T-cells, worsening CMV infection and making patients ineligible for CMV immunotherapy trials9. To address this unmet need, we will engineer CMV-specific T-cells in the laboratory to be glucocorticoid-resistant in order to bring CMV immunotherapy to patients with GvHD requiring glucocorticoids, hoping to reduce CMV-related morbidity, mortality, antiviral drug use and hospitalisation in this population.