Combining immunodiagnostics and immunotherapy for clinical management of infectious complications in transplant patients

Viral infections are an extremely common and predictable problem in organ and hematopoietic stem cell transplant patients. Antiviral drugs given either prophylactically or as early therapy for patients detected to be shedding virus appears to be an effective strategy for reducing herpes virus infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistance virus isolates ultimately resulting in treatment failure. Over the last few years, there is increasing evidence that cellular immune therapies can reverse the outgrowth of hematological malignancies and can also provide therapeutic benefit against lethal viral infections. While the expansion and adoptive transfer of virus-specific T-cells from the healthy original donor can be an effective strategy to control viral replication, this is not possible when donors are seronegative or are subsequently inaccessible. Studies from our group have demonstrated the successful expansion of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-specific T-cells from solid organ and stem cell transplant recipients with active viral infection or disease and the long term reconstitution of protective anti-viral immunity following their adoptive transfer back into the patients. More recently, we have also developed a single platform technology to extend this immunotherapeutic strategy for multiple pathogens including CMV, EBV, adenovirus and BK polyoma virus. T cells directed towards multiple pathogens can be rapidly expanded and can be used for adoptive immunotherapy. Finally, in collaboration with an Australian biotech company, Cellestis Inc., we have also developed a novel T cell-based immune monitoring technology (QuantiFERON-CMVâ) which will allow us to identify high risk transplant patients who may develop virus-associated complications post-transplantation.