Cellular immunotherapy for viral infection after HSC transplantation

Allogeneic haematopoietic stem cell (HSC) transplantation (HSCT) involves complete replacement of the blood and immune systems of the patient with those of the donor.HSCT is associated with marked immunosuppression, which extends for several months after transplantation until donor T cells can be generated de novo from donor HSCs in vivo. This leads to significant morbidity and mortality from bacterial and viral infections during the post-transplant period.Donor T cells can be transferred with the donor HSC graft at the time of transplantation, and these provide some protection against infection. However, these T cells can mediate graft-versus-host disease, so the number of T cells that is transferred is often reduced during HSC processing.Reactivation of latent herpesviruses, such as cytomegalovirus and Epstein–Barr virus, is a problem, and current antiviral agents do not provide complete protection against this. Reconstitution of a virus-specific immune response is required for sustained control of viral replication.If the transplant donor has immunity to a specific virus, antigen-specific T cells can be cultured from the donor and subsequently infused into the patient. This has been successfully carried out in a series of studies to control the replication of cytomegalovirus and Epstein–Barr virus.Techniques such as cytokine-secretion assays and the use of peptide–HLA tetramers allow the possibility of selecting antigen-specific T cells from the donor followed by direct infusion into the patient. These techniques have now been developed to clinical scale.Several regulatory issues need to be overcome if cellular immunotherapy is to fulfil its potential for the control of infectious disease.