Adoptive T cell therapy cures mice from active hemophagocytic lymphohistiocytosis (HLH).
adoptive T cell therapy
hemophagocytic lymphohistiocytosis
hyperinflammation
virus-specific T cells
Journal
EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: England
ID NLM: 101487380
Informations de publication
Date de publication:
07 12 2022
07 12 2022
Historique:
revised:
27
09
2022
received:
05
04
2022
accepted:
29
09
2022
pubmed:
25
10
2022
medline:
15
12
2022
entrez:
24
10
2022
Statut:
ppublish
Résumé
Primary hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by impaired lymphocyte cytotoxicity. First-line therapeutic regimens directed against activated immune cells or secreted cytokines show limited efficacy since they do not target the underlying immunological problem: defective lymphocyte cytotoxicity causing prolonged immune stimulation. A potential rescue strategy would be the adoptive transfer of ex vivo gene-corrected autologous T cells. However, transfusion of cytotoxicity-competent T cells under conditions of hyperinflammation may cause more harm than benefit. As a proof-of-concept for adoptive T cell therapy (ATCT) under hyperinflammatory conditions, we transferred syngeneic, cytotoxicity-competent T cells into mice with virally triggered active primary HLH. ATCT with functional syngeneic trigger-specific T cells cured Jinx mice from active HLH without life-threatening side effects and protected Perforin-deficient mice from lethal HLH progression by reconstituting cytotoxicity. Cured mice were protected long-term from HLH relapses. A threshold frequency of transferred T cells with functional differentiation was identified as a predictive biomarker for long-term survival. This study is the first proof-of-concept for ATCT in active HLH.
Identifiants
pubmed: 36278424
doi: 10.15252/emmm.202216085
pmc: PMC9728053
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16085Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.
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