ArticleEMBO molecular medicine2022
Adoptive T cell therapy cures mice from active hemophagocytic lymphohistiocytosis (HLH).
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Genotoxicity profiling reveals distinct platform-and cell type-specific effects in therapeutic gene editing for genetic hyperinflammation.Cell stem cell · 2026Article
- Histiocyte Society blueprint for hemophagocytic lymphohistiocytosis research: deciphering underlying disease mechanisms to optimize diagnosis and therapy.Haematologica · 2025Review
- The pathophysiology of hemophagocytic lympho-histiocytosis (HLH) syndrome and insights from animal models.Clinical and experimental immunology · 2025Review
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
- Tofacitinib for elderly onset hemophagocytic lymphohistiocytosis with gene mutations: a case report.MedComm · 2024Article
- Isolated Full Donor T-Cell Chimerism After Haploidentical TCRαβ/CD19 Depleted HSCT Maintains Remission of Familial HLH.Journal of clinical immunology · 2023Article
- Insights into the cellular pathophysiology of familial hemophagocytic lymphohistiocytosis.Frontiers in immunology · 2023Review
- Adoptive T cell therapy cures mice from active hemophagocytic lymphohistiocytosis (HLH).EMBO molecular medicine · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.