Adoptive T cell immunotherapy for cytomegalovirus

Abstract

Cytomegalovirus (CMV) is a major opportunistic pathogen following allogeneic transplantation, reflecting the inability of depressed host immunity to contain viral replication. Current antiviral drugs are limited by toxicities and lack of efficacy in established CMV disease, making adoptive immunotherapeutic strategies aimed at hastening virus-specific immune reconstitution attractive alternatives. A number of relatively small Phase I-II studies have demonstrated the feasibility of transferring CMV-specific T cells, varying in composition in terms of CD4+ and CD8+ T cell content. They have all suggested to varying degrees that restoration of CMV-specific immunity can be accelerated without an obvious effect on rates of graft-versus-host disease in those with CMV-seropositive donors. The majority also infer that recovery of laboratory measures of CMV-specific immunity correlate with clinical protection. Direct isolation of cells from donor blood now allows consideration of more widespread availability outside of a few academic centres, and equally importantly the delivery of randomised studies to establish the true efficacy of these strategies.