CAR-iNKT cells targeting clonal TCRVß chains as a precise strategy to treat T cell lymphoma.
Front Immunol
; 14: 1118681, 2023.
Article
em En
| MEDLINE
| ID: mdl-36936927
ABSTRACT
Introduction:
Most T cell receptor (TCR)Vß 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 TCRß 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 TCRVß 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-TCRVß CAR-iNKT cells.Results:
We show that anti-TCRVß 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-TCRVß CAR-T and -iNKT cell-based therapy of TCL with the latter providing the option for 'off-the-shelf' immunotherapy.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus Linfotrópico T Tipo 1 Humano
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Leucemia-Linfoma de Células T do Adulto
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Linfoma de Células T
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Linfoma de Células T Periférico
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Células T Matadoras Naturais
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Receptores de Antígenos Quiméricos
Limite:
Adult
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article