Anti-B7-H3 CAR-T celtherapie voor de behandeling van glioblastoom

Samenvatting

B7-H3 (CD276), a type I transmembrane protein that belongs to the B7-family, has gained interest as a cancer immunotherapy target. This is explained by its high expression on several human cancer types, while its expression on healthy tissues is absent or low. Among these cancers is glioblastoma (GBM), a difficult to cure cancer that is refractory to mainstream immunotherapies (e.g., blockade of CTLA-4 or PD-[L]1). It was recently shown that B7-H3-targeted chimeric antigen receptor (CAR)-T-cells were able to kill GBM-cells and patient-derived GBM-spheroids, encouraging their evaluation in phase I/II clinical trials. However, several topics merit further investigation to capitalize on the full potential of this adoptive cell therapy. B7-H3 is not a classical CAR-T-cell target, as it is an immune checkpoint ligand with potentially immune inhibitory and cancer-promoting activity. Gaining insight into the molecular pathways that are activated in T-cells and cancer cells as a result of a B7-H3-targeted T-cell attack could provide anchoring points to improve CAR-T-cell therapy. The design of the CAR is another point of attention as it impacts on therapy efficacy with nanobody-based CARs (nanoCARs) gaining increasing attention. In this project, these topics will be studied to develop a potent B7-H3-targeted nanoCAR-T-cell therapy to defeat GBM.

Datum prijs	25 jun. 2021
Originele taal	Dutch
Prijsuitreikende instantie	EC via Erasmus Hogeschool (EHB)
Begeleider	Fien Meeus (Advisor), Yannick De Vlaeminck (Co-promotor) & Karine Breckpot (Promotor)