Recent Developments in Cellular Immunotherapy for HSCT-Associated Complications

Abstract

Allogeneic hematopoietic stem cell transplantation is associated with serious complications, and improvement of the overall clinical outcome of patients with hematological malignancies is necessary. During the last decades, posttransplant donor-derived adoptive cellular immunotherapeutic strategies have been progressively developed for the treatment of graft-versus-host disease (GvHD), infectious complications, and tumor relapses. To date, the common challenge of all these cell-based approaches is their implementation for clinical application. Establishing an appropriate manufacturing process, to guarantee safe and effective therapeutics with simultaneous consideration of economic requirements is one of the most critical hurdles. In this review, we will discuss the recent scientific findings, clinical experiences, and technological advances for cell processing toward the application of mesenchymal stromal cells as a therapy for treatment of severe GvHD, virus-specific T cells for targeting life-threating infections, and of chimeric antigen receptors-engineered T cells to treat relapsed leukemia.

Mesenchymal stem cell-derived extracellular vesicles attenuate influenza virus-induced acute lung injury in a pig model

“…EVs are stable in circulation due to their lipid membrane, have no risk of aneuploidy, and are well tolerated in recipients due to their small size and lack of expression of MHC molecules. Moreover, EVs can be stored at -80°C without losing their biochemical activity [65,66]. Thus, EVs have the potential to become a safe and effective cell-free therapy for human diseases.…”

Successful Treatment of Adenovirus Infection with Brincidofovir in an Immunocompromised Patient after Hematological Stem Cell Transplantation

“…Adoptive immunotherapy by means of donor leukocyte infusion has been used, curing HAdV infection, but carries the risk of developing graft versus host reactions. erapies such as modified HAdV-specific T-cells are expensive and time consuming with complex administration procedures [12].…”

Infusion ofex-vivoexpanded human TCR-αβ+ double-negative regulatory T cells delays onset of xenogeneic graft-versus-host disease

“…Allogeneic haematopoietic stem cell transplantation (HSCT) is an effective treatment of haematopoietic malignancies, but graft-versus-host disease (GVHD) remains a major complication and the leading cause of non-relapse mortality [1,2]. Although patient survival has been improved in recent years, it is attributed mainly to advancements in the management of the symptoms rather than prevention of GVHD.…”