The Past and the Future of VSTs

Viral infections are major complications of Hematopoietic Stem Cell Transplantation (HSCT). As efficacy of anti-viral drugs is limited in absence of immune reconstitution and often associated with severe side effects, infusion of Virus-Specific T cells (VSTs) becomes a promising alternative treatment for viral infections and diseases after HSCT. A lot of improvement in VST generation has been made since 1992, date of first attempts. Regarding stimulation antigen, pools of peptides from viral immunodominant proteins become the best choice compared to whole proteins or other types of antigens. In respect with generation methods, a huge improvement has been done both with cell culture thanks to faster protocols of expansion and with immunomagnetic isolation thanks to fully automated generation of VSTs with a close system. This latest kind of VST generation is fast (within 24 hours), compliant with GMP guidelines and allows a wide distribution among cell therapy laboratories. Furthermore, cell source is no longer limited to the HSCT donor. Third-party donors either related or unrelated are also sought. A promising perspective could be the generation of CART based on VSTs aiming both at targeting the malignant cells and controlling the viral infections simultaneously.