αβ-T Cells Engineered to Express γδ-T Cell Receptors Can Kill Neuroblastoma Organoids Independent of MHC-I Expression

Josephine G.M. Strijker, Ronja Pscheid, Esther Drent, Jessica J.F. van der Hoek, Bianca Koopmans, Kimberley Ober, Sander R. van Hooff, Waleed M. Kholosy, Annelisa M. Cornel, Chris Coomans, Andrea Bisso, Marleen M. van Loenen, Jan J. Molenaar, Judith Wienke

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

2 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Artikelnummer923
TijdschriftJournal of Personalized Medicine
Volume11
Nummer van het tijdschrift9
DOI's
StatusGepubliceerd - sep. 2021

Vingerafdruk

Duik in de onderzoeksthema's van 'αβ-T Cells Engineered to Express γδ-T Cell Receptors Can Kill Neuroblastoma Organoids Independent of MHC-I Expression'. Samen vormen ze een unieke vingerafdruk.

Citeer dit