A5080084632- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Viral-associated cancers and disorders
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- Radiopharmaceutical Chemistry and Applications
- Nanoplatforms for cancer theranostics
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Occupational and environmental lung diseases
- Pleural and Pulmonary Diseases
- T-cell and Retrovirus Studies
- Parvovirus B19 Infection Studies
- Polyomavirus and related diseases
- Receptor Mechanisms and Signaling
- Herpesvirus Infections and Treatments
- Lymphoma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- PARP inhibition in cancer therapy
- Neuroblastoma Research and Treatments
- vaccines and immunoinformatics approaches
Molecular Partners (Switzerland)
2016-2023
Targovax (Norway)
2021-2023
Institute of Cytology and Genetics
2022
Siberian Branch of the Russian Academy of Sciences
2022
Roche (Switzerland)
2013-2016
Johns Hopkins Medicine
2009-2013
Johns Hopkins University
2009-2013
Karolinska Institutet
1994-2007
Center for Strategic Research
2006
National Center for Tumor Diseases
2004
Although malaria and Epstein–Barr (EBV) infection are recognized cofactors in the genesis of endemic Burkitt lymphoma (BL), their relative contribution is not understood. BL, most common paediatric cancer equatorial Africa, a high-grade B cell characterized by c-myc translocation. EBV ubiquitous lymphotropic virus that persists latent state after primary infection, children have sero-converted 3 y age. Malaria profoundly affects compartment, inducing polyclonal activation...
Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus of humans that elicits strong HLA class I-restricted cytotoxic T lymphocyte (CTL) responses. An influence such responses on evolution was first suggested by our finding EBV isolates from the highly A11-positive Papua New Guinea (PNG) population carried lys-thr mutation at residue 424 nuclear antigen EBV-encoded (EBNA4) destroyed immunodominant target epitope for A11-restricted CTL recognition. Here we turn to much larger population,...
We have investigated the reactivity to two human histocompatibility leukocyte antigen (HLA) A11-restricted cytotoxic T lymphocyte (CTL) epitopes derived from amino acids 416-424 (IVTDFSVIK, designated IVT) and 399-408 (AVFDRKSVAK, AVF) of Epstein-Barr virus (EBV) nuclear (EBNA) 4. A strong predominance CTL clones specific for IVT epitope was demonstrated in polyclonal cultures generated by stimulation lymphocytes EBV-seropositive donor BK with autologous B95.8 virus-transformed...
Cytolethal distending toxins (CDTs) block proliferation of mammalian cells by activating DNA damage-induced checkpoint responses. We demonstrate that the Haemophilus ducreyi CDT (HdCDT) induces phosphorylation histone H2AX as early 1 h after intoxication and re-localization repair complex Mre11 in HeLa with kinetics similar to those observed upon ionizing radiation. Early was dependent on a functional Ataxia Telangiectasia mutated (ATM) kinase. Microinjection His-tagged HdCdtB subunit,...
The T cell receptor (TCR) repertoires of cytotoxic responses to the immunodominant and subdominant HLA A11–restricted epitopes in Epstein-Barr virus (EBV) nuclear antigen-4 were investigated four healthy carriers. response epitope (EBNA4 399-408, designated AVF) was highly restricted with conserved Vβ usage identical length amino acid motifs third complementarity-determining regions (CDR3), while a broad repertoire using different combinations TCR-α/β V J segments CDR3 selected by 416-424,...
Benign prostatic hyperplasia (BPH) is a common chronic non-malignant condition whose prevalence substantially increases with age. Immune cell infiltration and pro-inflammatory mediators have been implicated in the pathogenesis. Here, we characterized 21 extracellular markers on prostate-infiltrating lymphocytes (PILs) analyzed expression of 26 soluble proteins prostate tissue obtained from BPH patients (n = 31). These data were correlated clinical parameters compared peripheral blood...
The CD40 receptor is an attractive target for cancer immunotherapy. Although a modest pharmacodynamic effect seen in patients following administration of CD40-targeting monoclonal antibodies (mAb), the doses that could be safely administered do not result meaningful clinical response, most likely due to limited therapeutic window associated with systemic activation. To overcome this issue, we developed multispecific DARPin construct, α-FAPxCD40, which has conditional activity at site...
Background ONCOS-102, an oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor, can alter the tumor microenvironment to immunostimulatory state. Combining ONCOS-102 with standard-of-care chemotherapy for malignant pleural mesothelioma (MPM) may improve treatment outcomes. Methods In this open-label, randomized study, patients unresectable MPM received intratumoral (3×10 11 virus particles on days 1, 4, 8, 36, 78, and 120) pemetrexed plus cisplatin/carboplatin (from...
Abstract Background Intratumoral injection of oncolytic viruses (OVs) shows promise in immunotherapy: ONCOS-102, a genetically engineered OV that encodes Granulocyte–Macrophage Colony-Stimulating Factor (GM-CSF) demonstrated efficacy early clinical trials, enhancing T cell infiltration tumors. This suggests OVs may boost various forms immunotherapy, including tumor-specific bi-specific antibodies (BsAbs). Methods Our study investigated vitro, how ONCOS-204, variant ONCOS-virus expressing the...
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus that involved in the pathogenesis of wide spectrum malignant and non-malignant diseases. Strong evidence implicates T lymphocytes control EBV replication tumorigenesis, but cellular components innate immune system are poorly characterized terms their function development EBV-specific immunity or interaction with virus. This study demonstrates virions produced epithelial cells surpass B cell-derived counterparts capacity to enter...
EBV is associated with a broad range of malignancies. Adoptive immunotherapy these tumors EBV-specific CTL proved useful. We generated panel primary human T cells specific to various antigens (i.e. Epstein–Barr nuclear antigen 3A, 3B and BamHI-M leftward reading frame) via transfer modified TCR genes that are either coupled CD3ζ or Fc(ε)RIγ. TCR-transduced from 20–60% donors (total number 25) demonstrated lysis peptide-loaded target cells, whereas lymphoblastoid cell lines expressing native...
The syntaxin 11 (STX11) gene is mutated in a proportion of patients with familial haemophagocytic lymphohistiocytosis (FHL) and exocytosis cytotoxic granules impaired STX11-deficient NK cells. However, the subcellular localization, regulation expression molecular function STX11 cells other lymphocytes remain unknown. Here we demonstrate that strictly controlled by several mechanisms cell-type-specific manner enzymatic activity proteasome required for In resting NKL cells, was localized...
Epstein-Barr virus (EBV) is a lymphotropic γ herpes virus. Infection of human B cells with EBV in vitro results their immortalization and the resulting cell lines are named lymphoblastoid (LCLs) (). In these cells, establishes mainly latent infection, characterized by expression limited number viral proteins. LCLs express 6 nuclear proteins (EBNA1 to 6), 3 membrane (LMP1, LMP2A, LMP2B) two small untranslated RNA molecules (EBER1 EBER2) (reviewed refs. , ). have phenotype highly activated as...
Abstract BACKGROUND Human prostate specific antigen (PSA) is expressed selectively in epithelium and a potential target for the immunotherapy against cancer. Various PSA‐based vaccines have been reported to induce cytotoxic T lymphocyte (CTL) responses animal models. Here, we present identification validation of an immunodominant CTL epitope PSA C57Bl/6 mice (H‐2 b ). METHODS PSA‐specific CTLs were induced by immunization with plasmid expressing PSA. Epitope specificity was determined their...
Immune checkpoint blockade has shown promising results in numerous cancer types. However, prostate (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from tissue patients with PC (n = 5), benign prostatic hyperplasia (BPH) 27), BPH concurrent 4) and controls 7). The majority were CD8+ had a CCR7-CD45RO+ effector memory phenotype. yield lesions was on average 20-fold higher than that obtained control...
EBV isolates from human populations with a high frequency of HLA A11 evade recognition by CTLs specific for an immunodominant A11-restricted epitope derived the nuclear antigen 4 (EBNA-4). We have previously described four nonimmunogenic variants this carrying single amino acid substitutions in anchor residues peptide. now investigated antigenicity, binding capacity, endoplasmic reticulum translocation, endogenous processing, and presentation these variants. The peptides were either unable...
Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in the liver is critical for vaccination-induced protection against malaria. While many intracellular pathogens subvert presentation machinery, its functionality course malaria hepatocytes has not been characterized. Using experimental systems based on specific identification, isolation and analysis human infected with P. berghei ANKA GFP or falciparum 3D7 sporozoites we demonstrated that molecular components...
PD-1/PD-L1 blockade has revolutionized the field of immunooncology. Despite relative success, response rate to anti-PD-1 therapy requires further improvements. Our aim was explore enhancement T-cell function by using novel PD-1-blocking proteins and compare with clinically approved monoclonal antibodies (mAbs). We isolated T-cells from ascites tumor 17 patients advanced epithelial ovarian cancer (EOC) analyzed effects mAbs nivolumab pembrolizumab two engineered ankyrin repeat (DARPin®...
The mechanisms of major histocompatibility complex (MHC) class I downregulation during Epstein-Barr virus (EBV) replication are not well characterized. Here we show that in several cell lines infected with a recombinant EBV strain encoding green fluorescent protein (GFP), the lytic cycle coincides GFP expression, which thus can be used as marker replication. resulted MHC II and all classical alleles independently viral DNA synthesis or late gene expression. Although assembled complexes,...
Limiting dilution assays (LDA) are designed to define an unknown frequency of effector cells in a population. LDA dose-response that allow detection all-or-none (positive or negative) immunoresponse each individual culture within replicates vary the number responder tested (reviewed ref. ). The positive cultures is not informative because it never clear whether one more precursors well giving response. negative response instead demonstrates there no given specificity. Therefore, evaluation...