The role of virus-specific adoptive T-cell therapy in hematopoietic transplantation

Viral infections are amongst the most significant complications following hematopoietic transplantation and occur principally because of a lack of virus-specific T cells. Drug treatments are often suboptimal because of toxicity, limited viral sensitivity, or the potential for the development of resistance. Adoptive immunotherapy to restore virus-specific cellular immunity is clearly an attractive alternative and the pioneering work of the previous decade established that cellular products could be clinically effective. However, the techniques used in these early studies are expensive and relatively difficult to produce to GMP-compliant standards. This is major limitation to their wider application. This review concentrates on more recent studies detailing direct selection methodologies that are more suited to clinical scalability and more readily assessable in prospective randomised studies. We will also consider strategies that allow multiple pathogens to be targeted concurrently, and strategies that aim to extend the benefits of these technologies to transplant recipients whose donors are seronegative for these viruses and currently are most vulnerable to viral reactivations.