Thesis Wesley Huisman

On 1 February 2024 (4:15 PM) Sanquin and LUMC researcher Wesley Huisman defended his thesis 'Risks and potential benefits of adoptively transferred virus-specific T cells' at Leiden University.

Promotores: Prof JHF Falkenburg PhD
Copromotores: I Jedema PhD and Prof D Amsen PhD
Venue: Leiden University, Academy Building

Summary

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.

Chapters

Chapter 1
General introduction and aims of the thesis

Chapter 2
Trackingthe progeny of adoptively transferred virus-specific T cel Is in patients posttransplant using TCR sequencing abstract

Chapter 3
Magnitude of off-target allo-HLA reactivity by third-party donor-derived virus-specific T cells is dictated by HLA- restriction abstract

Chapter 4
Public T-cell receptors (TCRs) revisited by analysis of the magnitude of identical and highly-similar TCRs in virus- specific T-cell repertoires of healthy individuals abstract

Chapter 5
Identification of functional HLA-A*01:01-restricted Epstein-Barr Latent Membrane Protein 2—specific T-cell receptors abstract

Chapter 6
Amino acids at position 5 in the peptide/MHC binding region of a public virus-specific TCR are completely inter- changeable without loss of function abstract

Chapter 7
Summary and general discussion

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