Hematopoietic stem cell transplantation (HSCT) is a curative procedure for many hematologic conditions, but it is often associated with life-threatening complications such as immune deficiency. As a result, numerous strategies for hastening immune reconstitution post-transplant are currently in development. One such strategy, termed adoptive T-cell transfer, has shown promise in reestablishing T-cell immunity in patients with refractory viral infections following allogeneic HSCT.
In a review article published in the Journal of Hematology & Oncology, Theresa Kaeuferle, of the department of pediatric hematology at the Dr von Hauner University Children’s Hospital in Germany, and colleagues summarized the current literature surrounding the development of adoptive T-cell transfer over the past 30 years.
“Approximately one-third of infection-related deaths [after transplantation] are caused by viruses, mainly human cytomegalovirus (CMV), Epstein-Barr virus (EBV), or human adenovirus (AdV),” the reviewers wrote.
The Process of Adoptive T-Cell Transfer
Early procedures for adoptive transfer of virus-specific T cells were established using donor lymphocyte infusions, which facilitated antiviral activity in immunocompromised patients. Despite encouraging preliminary results, the presence of alloreactive T cells greatly increased the risk for graft-versus-host disease (GVHD) in these patients. In response, various additional strategies have been created over the past 2 decades to improve the use of virus-specific T cells in transplant populations.
Two modern day approaches to adoptive transfer of virus-specific T lymphocytes include direct selection and in vitro stimulation and expansion of T cells. Initially, T cells are stimulated through the use of a viral protein, lysate, or antigen-presenting cell; high amounts of virus-specific T cells can then be obtained from a small volume of blood. Subsequently, the virus-specific T lymphocytes are isolated and can be infused into the patient, where they will multiply under normal bodily conditions.
“The generation of adoptive T-cell therapy for each single virus in a separate manufacturing process is time- and cost-consuming, [so] there are strong efforts to establish protocols for the generation of multivirus-specific T cells in one single step,” the reviewers wrote.
Several studies have examined the clinical applications of adoptive T-cell therapy using CMV-, EBV-, and AdV-specific T lymphocytes. More recently, studies have begun to explore the use of multivirus-specific T cells to fight viral infections post-transplant. Overall, findings from these preliminary analyses have been promising, with some data showing complete clearance of viral pathogen and major symptomatic improvement in patients.