dr. Nele Festjens (PhD)

Chimeric Antigen Receptor (CAR) T cell therapy uniquely can provide life-long protection against re-emergence upon clearance of even advanced-stage leukemia. However, for the more frequent solid tumor types (carcinomas, lymphomas), clearance of advanced-stage tumors, and especially the subsequent long-term protection, is only rarely achieved. The main reason for this is the multi-pathway immunosuppressive environment that these tumors evolve to overcome the selective pressure imposed by the patient’s immune system. This both hampers the initial attack by CAR-Ts, and often leads to low numbers of long-term persisting CAR-T cells, which tend to be in a state of functional exhaustion. Most attempts at overcoming this, target particular CAR-T cell proteins involved in individual pathways of immunosuppression. However, it is clear from early-stage clinical trials with such engineered CAR-T cells that multiple pathways will need to be tackled at the same time.
Inspired by this challenge, we have chosen a different path. As the glycans decorating the T cell surface are implicated in T cell activation, differentiation, proliferation, and in the interaction of human T cells with tumor cells, we study the role of human T cell glycosylation in more depth by manipulating the glycome of CAR-T cells. The unique property of glycosylation pathways is that they often modulate a large range of cell surface receptor biology at the same time.
We use CRISPR-Cas9 genome engineering to induce mutations/deletions in specific pathways in CAR-T cells. The structure and function of the altered CAR-T-cells is being investigated in vitro and in vivo in different mouse cancer models.
 

• Master in Biotechnology (UGent, 2000) 
• PhD in Biotechnology in the lab of prof. dr. Peter Vandenabeele (UGent, 2006) 
• Post-doctoral research fellow in the lab of prof. dr. Nico Callewaert (UGent, 2006-2007) 
• FWO post-doctoral research fellow in the lab of prof. dr. Nico Callewaert (2007-2014)
• Staff scientist in the lab of prof. dr Nico Callewaert (2014-June 2023)
• Sr Staff Scientist and Team Lead CAR-T cell genome engineering in the lab of prof. dr Nico Callewaert (July 2023- present)
   

• Dr Elien De Bousser (PhD) - postdoctoral researcher
• Laure De Pryck - doctoral fellow
• Ji-Yoon Sohn - doctoral fellow
• Evelyn Plets - technician
• Laura Vuylsteke - technician
   

• Human T cell glycosylation and implications on immune therapy for cancer. Hum. Vaccines Immunother. 16, 2374–2388 (2020).
• T Cell Engaging Immunotherapies, Highlighting Chimeric Antigen Receptor (CAR) T Cell Therapy. Cancers 13, 6067 (2021).
• N-glycosylation engineering in chimeric antigen receptor T cells enhances anti-tumor activity. bioRxiv (2023) doi:https://doi.org/10.1101/2023.01.23.525164.
• Patent W0 2023/111322 A2. Glyco-engineered CAR-T Cells. (2023).
  
   

• Lab address: Technologiepark 75, 9052 Zwijnaarde (Belgium)
• LinkedIn 
• ORCID ID 
• VIB-Ugent Center for Medical Biotechnology