In this section
@article{Rowan:2023:10.3389/fimmu.2023.1118681,
author = {Rowan, A and Ponnusamy, K and Ren, H and Taylor, G and Cook, L and Karadimitris, A},
doi = {10.3389/fimmu.2023.1118681},
journal = {Frontiers in Immunology},
pages = {1--11},
title = {CAR-iNKT cells targeting clonal TCRVβ chains as a precise strategy to treat T cell lymphoma},
url = {http://dx.doi.org/10.3389/fimmu.2023.1118681},
volume = {14},
year = {2023}
}
TY - JOUR
AB - Introduction: Most T cell receptor (TCR)Vβ chain-expressing T cell lymphomas (TCL) including those caused by Human T cell leukaemia virus type-1 (HTLV-1) have poor prognosis. We hypothesised that chimeric antigen receptor (CAR)-mediated targeting of the clonal, lymphoma-associated TCRβ chains would comprise an effective cell therapy for TCL that would minimally impact the physiological TCR repertoire.Methods: As proof of concept, we generated CAR constructs to target four TCRVβ subunits. Efficacy of the CAR constructs was tested using conventional T cells as effectors (CAR-T). Since invariant NKT (iNKT) cell do not incite acute graft-versus-host disease and are suitable for ‘off-the-shelf’ immunotherapy, we generated anti-TCRVβ CAR-iNKT cells.Results: We show that anti-TCRVβ CAR-T cells selectively kill their cognate tumour targets while leaving >90% of the physiological TCR repertoire intact. CAR-iNKT cells inhibited the growth of TCL in vivo, and were also selectively active against malignant cells from Adult T cell leukaemia/lymphoma patients without activating expression of HTLV-1.Discussion: Thus we provide proof-of-concept for effective and selective anti-TCRVβ CAR-T and -iNKT cell-based therapy of TCL with the latter providing the option for ‘off-the-shelf’ immunotherapy.
AU - Rowan,A
AU - Ponnusamy,K
AU - Ren,H
AU - Taylor,G
AU - Cook,L
AU - Karadimitris,A
DO - 10.3389/fimmu.2023.1118681
EP - 11
PY - 2023///
SN - 1664-3224
SP - 1
TI - CAR-iNKT cells targeting clonal TCRVβ chains as a precise strategy to treat T cell lymphoma
T2 - Frontiers in Immunology
UR - http://dx.doi.org/10.3389/fimmu.2023.1118681
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2023.1118681/full
VL - 14
ER -