Doctoral fellow – Lab of Pharmaceutical Biotechnology, Department of Pharmaceutics (Faculty of Pharmaceutical Sciences, UGent)
Principal investigator: prof. Filip Van Nieuwerburgh (PhD)
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and represents the most aggressive and challenging subtype to manage. The introduction of immune checkpoint inhibitors (ICIs) in the beginning of the previous decade has provided a promising new class of therapeutics to treat TNBC. However, for ICIs to work effectively, it is key that the patient must have reactive T-cells present in the tumor micro environment (TME). In most solid cancer TMEs, myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) foster immunosuppression, and thereby diminish the efficacy of ICIs. Targeting TAMs and MDSCs to halt their role in tumor progression therefore presents a novel strategy to bolster ICI therapies, especially in 'cold' TMEs. Our research focusses on the development of a gene editing strategy to knock out the signal regulatory protein-alpha (SIRP-α) receptor, present on MDSCs and TAMs, in order to create long-lasting anti-tumor immune responses. Lipid nanoparticles (LNPs) are currently one of the most popular and sophisticated nonviral delivery platforms and therefore seem extremely suitable for this research. However, the impact of LNP composition on its delivery mechanisms remains inadequately understood, posing a critical knowledge gap in this field.
The goal of our research will therefore be to elucidate the correlation between LNP design and its resulting biodistribution and cellular tropism towards MDSCs and TAMs. We plan to employ a DNA-barcoding and sequencing-based methodology to precisely elucidate these associations. This knowledge will then be used for in situ CRISPR-mediated silencing of SIRP-α in myeloid cells in a syngeneic orthotopic TNB cancer model. We will evaluate the therapeutic efficacy, with and without concurrent anti-PD-1 treatment.
- Bachelor of Science in Pharmaceutical Sciences
- Master of Science in Pharmaceutical Sciences – Drug Development
- Master of Science in de Industrial Pharmacy
Contact & links
- Lab address: Laboratory of Pharmaceutical Biotechnology, Campus Heymans, Ottergemsesteenweg 460, B - 9000 Ghent, Belgium
- Aaron Verplancke is interested to receive invitations for presentations or talks