Risks and potential benefits of adoptively transferred virus-specific T cells

Huisman, W. (2024)

Doctoral Thesis

Virus-specific T cells play a key role in the control of viral-reactivations in healthy individuals and this cellular immunity is impaired in patients receiving allogeneic stem cell transplantation. In the period around the transplantation, donor-derived T cells are either depleted or suppressed to reduce the risk of graft versus host disease (GVHD). However, in the absence of donor-derived T cells, latent viruses such as CMV, EBV and AdV can reactivate and remain uncontrolled and at the same time the curative graft versus leukemia (GVL) effect is abrogated. Therefore, the major challenge in the field of alloSCT is to find a balance between the GVL effect, protection against viruses and GVHD. The research described in this thesis focusses on the options to control for viral reactivations using adoptive transfer of virus-specific T cells or TCRs and the risks associated with this.

• Adoptive transfer
• TCR-sequencing
• Virus-specific T cells
• Allo-HLA cross-reactivity
• Off-target reactivity
• T-cell receptors

• All authors: Huisman, W.
• Supervisor: Falkenburg, J.H.F.
• Co-supervisor: Jedema, I.; Amsen, D.
• Committee: Ossendorp, F.A.; Schumacher, A.N.M.; Lier, R.A.W. van; Schoot, C.E. van der
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2024-02-01
• ISBN (print): 9789464960105
• Sponsorship: Sanquin