| Autor: |
Strijker JGM; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Pscheid R; Gadeta B.V., 3584 CM Utrecht, The Netherlands., Drent E; Gadeta B.V., 3584 CM Utrecht, The Netherlands., van der Hoek JJF; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Koopmans B; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Ober K; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., van Hooff SR; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Kholosy WM; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Cornel AM; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands.; University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands., Coomans C; Gadeta B.V., 3584 CM Utrecht, The Netherlands., Bisso A; Gadeta B.V., 3584 CM Utrecht, The Netherlands., van Loenen MM; Gadeta B.V., 3584 CM Utrecht, The Netherlands., Molenaar JJ; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands., Wienke J; Princess Máxima Center for Pediatric Oncology, 3584 CS Utrecht, The Netherlands. |
| Abstrakt: |
Currently ~50% of patients with a diagnosis of high-risk neuroblastoma will not survive due to relapsing or refractory disease. Recent innovations in immunotherapy for solid tumors are highly promising, but the low MHC-I expression of neuroblastoma represents a major challenge for T cell-mediated immunotherapy. Here, we propose a novel T cell-based immunotherapy approach for neuroblastoma, based on the use of TEG002, αβ-T cells engineered to express a defined γδ-T cell receptor, which can recognize and kill target cells independent of MHC-I. In a co-culture killing assay, we showed that 3 out of 6 neuroblastoma organoids could activate TEG002 as measured by IFNγ production. Transcriptional profiling showed this effect correlates with an increased activity of processes involved in interferon signaling and extracellular matrix organization. Analysis of the dynamics of organoid killing by TEG002 over time confirmed that organoids which induced TEG002 activation were efficiently killed independent of their MHC-I expression. Of note, efficacy of TEG002 treatment was superior to donor-matched untransduced αβ-T cells or endogenous γδ-T cells. Our data suggest that TEG002 may be a promising novel treatment option for a subset of neuroblastoma patients. |
