A5072640833- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Autoimmune and Inflammatory Disorders Research
- T-cell and B-cell Immunology
- Parvovirus B19 Infection Studies
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Lysosomal Storage Disorders Research
- Hematopoietic Stem Cell Transplantation
- Viral-associated cancers and disorders
- Acute Myeloid Leukemia Research
Oslo University Hospital
2023-2025
University of Oslo
2023-2025
Karolinska Institutet
2019-2025
Coalition for Epidemic Preparedness Innovations
2024
Public Risk Management Association
2023
Karolinska University Hospital
2019-2020
Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated cells and associated with a variable clinical spectrum having overlap more common pathophysiologies. HLH difficult diagnose can be part inflammatory syndromes. Here, we identify novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients superimposable features, including neonatal-onset cytopenia dyshematopoiesis, autoinflammation,...
Transforming growth factor beta (TGFβ) and activin A suppress natural killer (NK) cell function proliferation, limiting the efficacy of adoptive NK therapies. Inspired by partial resistance to TGFβ cells with SMAD4 haploinsufficiency, we used CRISPR–Cas9 for knockout in human cells. Here show that SMAD4KO were resistant inhibition, retaining their cytotoxicity, cytokine secretion interleukin-2/interleukin-15-driven proliferation. They showed enhanced tumor penetration control, both as...
Abstract Autosomal recessive mutations in RAB27A are associated with Griscelli syndrome type 2 (GS2), characterized by hypopigmentation and development of early-onset, potentially fatal hemophagocytic lymphohistiocytosis (HLH). We describe a 35-year old male who presented recurrent fever, was diagnosed Epstein-Barr virus-driven chronic lymphoproliferation, fulfilled clinical HLH criteria, carried novel homozygous c.551G > A p.(R184Q) variant. aimed to evaluate the contribution identified...
Autosomal recessive mutations in genes required for cytotoxicity are causative of a life-threatening, early-onset hyperinflammatory syndrome termed familial hemophagocytic lymphohistiocytosis (FHL). Mutations UNC13D cause FHL type 3. encodes Munc13-4, member the Unc13 protein family which control SNARE complex formation and vesicle fusion. We have previously identified FHL3-associated first intron transcription from an alternative transcriptional start site. Using isoform specific...
Abstract Mutations in SH2D1A , encoding the intracellular adaptor signaling lymphocyte activation molecule associated protein (SAP), are with X‐linked lymphoproliferative disease type 1 (XLP1). We identified a novel hemizygous c.49G > A (p.E17K) variant 21‐year‐old patient fatal Epstein‐Barr virus infection–associated hemophagocytic lymphohistiocytosis. Cellular and biochemical assays revealed normal expression of SAP protein, yet binding to phosphorylated CD244 receptor was reduced by...
<h3>Background</h3> ADAPT-NK cells are GMP-compliant, in vitro expanded adaptive NK cells, which naturally develop cytomegalovirus-positive individuals. This cell therapy platform harnesses the enhanced functional capabilities of and has shown superior anti-tumor properties due to expression activating NKG2C receptor, binds HLA-E liquid solid tumors, presence a single-KIR making them suited for transfer across HLA barriers. To further improve therapeutic potential we investigated genetic...
<h3>Background</h3> Differences in the persistence and anti-tumor responses of various NK cell subsets represent key hurdles to implementation cell-based cancer immunotherapies. Our lab has recently developed a protocol for specific expansion adaptive subpopulation.<sup>1</sup> Due their unique KIR repertoire with dominant expression one single KIR, cells deliver strong, predictable missing-self response an allogeneic, HLA-C/KIR mismatch setting. However, allorejection may significantly...
<h3>Background</h3> HLA-E is overexpressed by approximately 80% of solid tumors, including malignant glioblastoma and emerging as a major check point turning NKG2A+ CD8 T cells NK in the tumor microenvironment circulation.<sup>1 2</sup> This axis operates side-by-side with PD-L1 to block both cells.<sup>3</sup> Blockade this suppressive pathway unleashes cytotoxic lymphocytes prevents metastasis.<sup>1</sup> notion supported CRISPR screens mice, identifying Qa-1 (the mouse orthologue HLA-E)...
Abstract HLA-E is overexpressed by approximately 80% of solid tumors, including malignant glioblastoma, and emerging as a major checkpoint for NKG2A + CD8 T cells NK in the tumor microenvironment circulation. This axis operates side-by-side with PD-L1 to shut down effector responses cells. Here, we engineered novel chimeric A/C switch receptor, combining strong binding affinity receptor ectodomain activating signaling NKG2C endodomain. We found that Switch-transduced displayed superior...