A5023792974- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Viral Infectious Diseases and Gene Expression in Insects
- Protein Tyrosine Phosphatases
- Cellular transport and secretion
- Toxin Mechanisms and Immunotoxins
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Nanowire Synthesis and Applications
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Transgenic Plants and Applications
- CRISPR and Genetic Engineering
- vaccines and immunoinformatics approaches
- Lymphoma Diagnosis and Treatment
- Endoplasmic Reticulum Stress and Disease
- Lipid Membrane Structure and Behavior
- Cancer Research and Treatments
- Chronic Lymphocytic Leukemia Research
- Advanced biosensing and bioanalysis techniques
- Glycosylation and Glycoproteins Research
- Escherichia coli research studies
Oslo University Hospital
2015-2024
University of Oslo
2006-2019
Cellular Therapeutics (United Kingdom)
2019
Norwegian Cancer Society
2004-2017
Foundation for laboratory medicine
2007
University of Geneva
2007
Prion diseases are transmissible neurodegenerative disorders characterized by extensive neuronal apoptosis and accumulation of misfolded prion protein (PrP SC ). Recent reports indicate that PrP induces via activation the endoplasmic reticulum (ER) stress pathway ER resident caspase-12. Here, we investigate relationship between replication induction during different stages disease in a murine scrapie model. The first alteration observed consists upregulation chaperone glucose-regulated...
The endosomal sorting complexes required for transport, ESCRT-I, -II, and -III, are thought to mediate the biogenesis of multivesicular endosomes (MVEs) ubiquitinated membrane proteins. Here, we have compared importance ESCRT-I subunit tumor susceptibility gene 101 (Tsg101) ESCRT-III hVps24/CHMP3 functions receptor signaling. Like Tsg101, endogenous hVps24 localized mainly late endosomes. Depletion by siRNA showed that this ESCRT subunit, like is important degradation epidermal growth factor...
Abstract Currently the greatest challenge in oncology is lack of homogeneity lesions where different cell components respond differently to treatment. There growing consensus that monotherapies are insufficient eradicate disease and there an unmet need for more potent combinatorial treatments. We have previously shown hypericin photodynamic therapy (HYP-PDT) triggers electron transport chain (ETC) inhibition mitochondria. also tamoxifen (TAM) enhances cytotoxicity cells with high...
Checkpoint blockade can reverse T-cell exhaustion and promote antitumor responses. Although blocking the PD-1 pathway has been successful in Hodgkin lymphoma, response rates have modest B-cell non-Hodgkin lymphoma (NHL). Coblockade of checkpoint receptors may therefore be necessary to optimize Here, characterization coinhibitory receptor expression intratumoral T cells from different NHL types identified TIGIT as frequently expressed receptors. Tumors patients were enriched CD8+ CD4+...
The BCR consists of surface-bound Ig and a heterodimeric signaling unit comprised CD79A CD79B. Upon cognate Ag recognition, the receptor initiates important signals for B cell development function. also conveys Ag-independent survival termed tonic signaling. Although requirement CD79A/CD79B heterodimer complex assembly surface expression is well established based on mice models, few studies have investigated this in human mature cells. In study, we found that tonsillar cells with high IgM or...
Immune checkpoint inhibitors and chimeric antigen receptor (CAR)-based therapies have transformed cancer treatment. Recently, combining these approaches into a strategy of PD-L1-targeted CAR has been proposed to target PD-L1high tumors. Our study provides new information on the efficacy such an approach against PD-L1low targets.New atezolizumab-based was generated introduced T, NK, or NK-92 cells. Breast MDA-MB-231 MCF-7 cell lines non-malignant cells (HEK293T, HMEC, MCF-10A, BM-MSC) were...
Many pharmacologically important receptors, including all cytokine signal via tyrosine (auto)phosphorylation, followed by resetting to their original state through the action of protein phosphatases (PTPs). Establishing specificity PTPs for receptor substrates is critical both understanding how signaling regulated and development specific PTP inhibitors that act as ligand mimetics. We have set up a systematic approach finding are validated this with insulin kinase. tested nearly known human...
Effector T cells equipped with engineered antigen receptors specific for cancer targets have proven to be very efficient. Two methods emerged: the Chimeric Antigen Receptors (CARs) and T-cell Receptor (TCR) redirection. Although potent, CAR recognition is limited membrane antigens which represent around 1% of total proteins expressed, whereas TCRs advantage targeting any peptide resulting from cellular protein degradation. However, depend on heavy signalling machinery only present in...
Although chemo-immunotherapy has led to an improved overall survival for most B-cell lymphoma types, relapsed and refractory disease remains a challenge. The malaria drug artesunate previously been identified as growth suppressor in some cancer types was tested new treatment option lymphoma.We included sensitivity screen B cell lines. preclinical properties of single agent vitro 18 lines representing different histologies vivo aggressive xenograft model, using NSG mice. Artesunate-treated...
Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing in a tailor-made setting is long and expensive process which could be resolved by use universal cells. Currently, only Natural Killer (NK) cell line NK-92 FDA approved for use. In order expand their recognition ability, they were equipped with Chimeric Antigen Receptors (CARs). However, unlike CARs,...
Abstract Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic recurrent disease. Immunotherapies OS are not as promising some other cancer types due to intra-tumor heterogeneity considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform alkaline phosphatase, ALPL-1, which is highly specifically expressed primary OS. The...
T-cell receptor (TCR) transfer is an attractive strategy to increase the number of cancer-specific T cells in adoptive cell therapy. However, recent clinical and pre-clinical findings indicate that careful consideration target antigen required limit risk off-target toxicity. Directing against mutated proteins such as frequently occurring frameshift mutations may thus be a safer alternative tumor-associated self-antigens. Furthermore, result novel polypeptides allowing selection TCRs from...
T cells modified to express chimeric antigen receptor (CAR) targeting CD19 (CD19CAR) have produced remarkable clinical responses in patients with relapsed/refractory B-cell acute lymphoblastic leukemia. CD19CAR T-cell therapy has also demonstrated prominent effects non-Hodgkin lymphoma (B-NHL) patients. However, a subset of who relapse after outgrowth CD19- tumor cells. Hence, development alternative CARs other markers represents an unmet medical need for leukemia and B-NHL. Here, we...
Acute myeloid leukemia (AML) is characterized by the accumulation of immature cells in bone marrow and peripheral blood. Nearly half AML patients relapse after standard induction therapy, new forms therapy are urgently needed. Chimeric antigen receptor (CAR) T has so far not been successful due to lack efficacy safety. Indeed, most attractive targets stem cell markers such as CD33 or CD123. We demonstrate that CD37, a mature B marker, expressed samples, its presence correlates with European...
Abstract CD19-CAR-T-cells emerge as a major therapeutic option for relapsed/refractory B-cell-derived malignancies, however approximately half of patients eventually relapse. To identify resistance-driving factors, we repeatedly exposed B-cell lymphoma/B-cell acute lymphoblastic leukemia to 4-1BB/CD28-based in vitro . Generated models revealed costimulatory domain-dependent differences CD19 loss. While CD19-4-1BB-CAR-T-cells induced combination epitope/total protein loss,...
Ricin is transported from early endosomes and/or the recycling compartment to trans-Golgi network (TGN) and subsequently endoplasmic recticulum (ER) before it enters cytosol intoxicates cells. We have investigated role of Rab6 isoforms in retrograde transport ricin using both oligo- vector-based RNAi assays. TGN was inhibited by depletion Rab6A when messenger RNA (mRNA) levels were reduced more than 40% less 75%. However, mRNA 75% Rab6A' simultaneously up-regulated, inhibition sulfation...
Shiga toxin (Stx) is composed of an A-moiety that inhibits protein synthesis after translocation into the cytosol, and a B-moiety binds to Gb3 at cell surface mediates endocytosis toxin. After endocytosis, Stx transported retrogradely endoplasmic reticulum, then A-fragment enters cytosol. In this study, we have investigated whether toxin-induced signaling involved in its entry. was found activate Syk induce rapid tyrosine phosphorylation several proteins, one being clathrin heavy chain....
The plant toxin ricin is transported retrogradely from the cell surface to endoplasmic reticulum (ER) where enzymatically active part retrotranslocated cytosol, presumably by same mechanism as used misfolded proteins. ER degradation enhancing alpha-mannosidase I-like protein, EDEM, responsible for directing aberrant proteins ER-associated protein degradation. In this study, we have investigated whether EDEM involved in retrotranslocation. Overexpression of strongly protects against ricin....
Shiga toxin binds to globotriaosylceramide (Gb3) receptors on the target cell surface. To enter cytosol, is dependent endocytic uptake, retrograde transport Golgi apparatus and further endoplasmic reticulum before translocation of enzymatically active moiety cytosol. Here, we have investigated importance newly synthesized glycosphingolipids for uptake intracellular in HEp-2 cells. Inhibition glycosphingolipid synthesis by treatment with either PDMP or Fumonisin B(1) 24-48 h strongly reduced...
Fibroblast growth factor 1 ( FGF 1) taken up by cells into endocytic vesicles can be translocated across vesicular membranes the cytosol and nucleus where it has a regulatory activity. Previously, leucine‐rich repeat containing 59 LRRC 59) was identified as an intracellular binding partner of 1, but its biological role remained unknown. Here, we show that is strictly required for nuclear import exogenous 1. siRNA ‐mediated depletion did not inhibit translocation cytosol, blocked We also...