- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- TGF-β signaling in diseases
- Cancer Genomics and Diagnostics
- Cell death mechanisms and regulation
- Hematopoietic Stem Cell Transplantation
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Response and Inflammation
- Erythrocyte Function and Pathophysiology
- Phagocytosis and Immune Regulation
- Viral-associated cancers and disorders
- Biosimilars and Bioanalytical Methods
- Single-cell and spatial transcriptomics
- Immunodeficiency and Autoimmune Disorders
- Genetic factors in colorectal cancer
- Virus-based gene therapy research
- Nanowire Synthesis and Applications
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Blood disorders and treatments
Oslo University Hospital
2015-2024
University of Oslo
2015-2024
Cancer Registry of Norway
2023
Norwegian Cancer Society
1997-2021
Stanford University
2008-2016
Palo Alto University
2010
Hipple Cancer Research Center
1996
Abstract Insufficient reactivity against cells with low antigen density has emerged as an important cause of chimeric receptor (CAR) T-cell resistance. Little is known about factors that modulate the threshold for recognition. We demonstrate CD19 CAR activity dependent upon and construct in axicabtagene ciloleucel (CD19-CD28ζ) outperforms tisagenlecleucel (CD19-4-1BBζ) antigen-low tumors. Enhancing signal strength by including additional immunoreceptor tyrosine-based activation motifs (ITAM)...
Human tumors contain populations of both cancerous and host immune cells whose malignant signaling interactions may define each patient's disease trajectory. We used multiplexed phospho-flow cytometry to profile single within human follicular lymphoma discovered a subpopulation with impaired B cell antigen receptor (BCR) signaling. The abundance BCR-insensitive in tumor negatively correlated overall patient survival. These negative prognostic (LNP) increased as relapsed following...
Abstract We have characterized several stages of normal human B cell development in adult bone marrow by gene expression profiling hemopoietic stem cells, early (E-B), pro-B, pre-B, and immature using RNA amplification Lymphochip cDNA microarrays (n = 6). Hierarchical clustering 758 differentially expressed genes clearly separated the five populations. used sets to investigate functional assignment genes. Genes involved VDJ recombination as well lineage-associated transcription factors (TCF3...
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+...
Purpose: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing coinhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets.Experimental Design: Surface of 9 receptors governing function was characterized from lymph node healthy donor tonsils peripheral blood samples, using high-dimensional flow cytometry. The results...
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...
The recently cloned murine flt3 ligand (FL) was studied for its ability to stimulate the growth of primitive (Lin-Sca-1+) and more committed (Lin-Sca-1-) bone marrow progenitor cells, alone in combination with other hematopoietic factors (HGFs). Whereas FL a weak proliferative stimulator alone, it potently synergized number HGFs, including all four colony-stimulating factor (CSF), interleukin (IL) 6, IL-11, IL-12, stem cell (SCF), promote colony formation Lin-Sca-1+, but not Lin-Sca-1- or...
Mutant p21-ras proteins contain sequences that distinguish them from normal ras, and represent unique epitopes for T-cell recognition of antigen-bearing tumour cells. Here, we examined the capacity CD4+ CD8+ T cells, generated simultaneously by mutant-ras-peptide vaccination a pancreatic-adenocarcinoma patient, to recognize lyse autologous cells harbouring corresponding activated K-ras epitopes. The patient was vaccinated with purified 17mer ras peptide (KLVVVGAVGVGKSALTI), containing Gly12...
Abstract The S100A4 protein, which is involved in the metastasis process, a member of S100 superfamily Ca‐binding proteins. Members this family are multifunctional signaling proteins with dual extra and intracellular functions regulation diverse cellular processes. Several studies have established correlation between protein expression worse prognosis for patients various malignancies including breast cancer. In article, we used specific antibodies combination immunohistochemistry (IHC) to...
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,...
Summary The tumour microenvironment influences outcome in patients with follicular lymphoma ( FL ), but its impact on transformation is less studied. We investigated the prognostic significance of and survival treated rituximab era. examined diagnostic transformed biopsies from 52 using antibodies against CD 3, 4, 8, 21 CR 2), 57 (B3 GAT 1), 68, FOXP TIA 1, PD ‐1 PDCD ‐L1 274) PAX 5. Results were compared a second cohort 40 without signs during minimum five years observation time. Cell...
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...
Follicular lymphoma (FL) is the most common indolent type of B-cell non-Hodgkin lymphoma. Advances in treatment have improved overall survival, but early relapse or transformation to aggressive disease associated with inferior outcome. To identify genetic events and track tumor clonal evolution, we performed multi-omics analysis 94 longitudinal biopsies from 44 FL patients; 22 (tFL) without (nFL). Deep whole-exome sequencing confirmed recurrent mutations genes encoding epigenetic regulators...
During B- and T-cell ontogeny, extensive apoptosis occurs at distinct stages of development. Agents that increase intracellular levels cAMP induce in thymocytes mature B cells, prompting us to investigate the role signaling human CD10+ B-precursor cells. We show for first time forskolin (which increases cAMP) CD10- cells a dose-dependent manner (19%-94% with 0-1,000 microM after 48 hours incubation, IC50 = 150 microM). High were also obtained by exposing analogue 8-chlorophenylthio-cAMP...