A5040576999- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- T-cell and B-cell Immunology
- Pancreatic and Hepatic Oncology Research
- Galectins and Cancer Biology
- Caveolin-1 and cellular processes
- Macrophage Migration Inhibitory Factor
- Ovarian cancer diagnosis and treatment
- Eosinophilic Disorders and Syndromes
- FOXO transcription factor regulation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
Copenhagen University Hospital
2019-2022
University of Copenhagen
2020-2022
Herlev Hospital
2019-2022
Novo Nordisk Foundation
2020
Abstract Anti-programmed death (PD)-1 (aPD1) therapy is an effective treatment for metastatic melanoma (MM); however, over 50% of patients progress due to resistance. We tested a first-in-class immune-modulatory vaccine (IO102/IO103) against indoleamine 2,3-dioxygenase (IDO) and PD ligand 1 (PD-L1), targeting immunosuppressive cells tumor expressing IDO and/or PD-L1 (IDO/PD-L1), combined with nivolumab. Thirty aPD1 therapy-naive MM were treated in phase 1/2 study (...
Expression of the L-arginine catabolizing enzyme arginase 1 (ARG1) is a central immunosuppressive mechanism mediated by tumor-educated myeloid cells. Increased activity ARG1 promotes formation an microenvironment and leads to more aggressive phenotype in many cancers. Intrinsic T-cell immunity against ARG1-derived epitopes peripheral blood cancer patients healthy subjects has previously been demonstrated. To evaluate antitumor efficacy peptide vaccines as monotherapy combinational therapy...
Pancreatic ductal adenocarcinoma (PDAC) is associated with very poor survival, making it the third and fourth leading cause of all cancer-related deaths in USA European Union, respectively. The tumor microenvironment (TME) PDAC highly immunosuppressive desmoplastic, which could explain limited therapeutic effect immunotherapy PDAC. One key molecules that contributes to immunosuppression fibrosis transforming growth factor-β (TGFβ). aim this study was target fibrotic TME using a novel immune...
The mutant protein FOXL2C134W is expressed in at least 95% of adult-type ovarian granulosa cell tumors (AGCT) and considered to be a driver oncogenesis this disease. However, the molecular mechanism by which contributes tumorigenesis not known. Here, we show that acquires ability bind SMAD4, forming FOXL2C134W/SMAD4/SMAD2/3 complex binds novel hybrid DNA motif AGHCAHAA, unique mutant. This binding induced an enhancer-like chromatin state, leading transcription nearby genes, many are...
The calreticulin (CALR) exon 9 mutations that are identified in 20% of patients with Philadelphia chromosome negative chronic myeloproliferative neoplasms (MPN) generate immunogenic antigens. Thus, therapeutic cancer vaccination against mutant CALR could be a new treatment modality CALR-mutant MPN.The safety and efficacy the peptide CALRLong36 derived from was tested phase I clinical trial montanide as adjuvant. Ten CALRmut MPN were included received 15 vaccines over course one year. primary...
One way that tumors evade immune destruction is through tumor and stromal cell expression of arginine-degrading enzyme arginase-2 (ARG2). Here we describe the existence pro-inflammatory effector T-cells recognize ARG2 can directly target tumor-infiltrating cells. Using a library 34 peptides covering entire sequence, examined reactivity toward these in peripheral blood mononuclear cells from cancer patients healthy individuals. Interferon-γ ELISPOT revealed frequent responses against several...
Galectin-3 (Gal3) can be expressed by many cells in the tumor microenvironment (TME), including cancer cells, cancer-associated fibroblasts, tumor-associated macrophages, and regulatory T (Tregs). In addition to immunosuppression, Gal3 expression has been connected malignant cell transformation, progression, metastasis. present study, we found spontaneous T-cell responses against Gal3-derived peptides PBMCs from both healthy donors patients. We isolated expanded these Gal3-specific vitro...
High expression of the metabolic enzyme arginase-2 (ARG2) by cancer cells, regulatory immune or cells tumor stroma can reduce availability arginine (L-Arg) in microenvironment (TME). Depletion L-Arg has detrimental consequences for T and leads to T-cell dysfunction suppression anticancer responses. Previous work from our group demonstrated presence proinflammatory ARG2-specific CD4 that inhibited growth murine models on activation with ARG2-derived peptides. In this study, we investigated...
Chronic lymphocytic leukemia (CLL) patients with unmutated immunoglobulin heavy chain (IgHV) are at risk of early disease progression compared to mutated IgHV. As a preventive strategy, we treated 19 previously untreated CLL IgHV in phase 1/2 trial (clinicaltrials.gov, NCT03939234) exploring the efficacy and toxicity therapeutic cancer vaccine containing peptides derived from programmed death ligand 1 (PD-L1) 2 (PD-L2), hoping restore immunological control disease. According International...
Cells in the tumor microenvironment of Follicular lymphoma (FL) express checkpoint molecules such as programmed death ligands 1 and 2 (PD-L1 PD-L2) are suppressing anti-tumor immune activity. Stimulation peripheral blood mononuclear cells (PBMC) with PD-L1 (IO103) or PD-L2 (IO120) peptides can activate specific T inducing anti-regulatory functions including cytotoxicity against PD-L1/PD-L2-expressing cells. In this study, we vaccinated eight FL patients following treatment standard...
<div>Abstract<p>Expression of the L-arginine catabolizing enzyme arginase 1 (ARG1) is a central immunosuppressive mechanism mediated by tumor-educated myeloid cells. Increased activity ARG1 promotes formation an microenvironment and leads to more aggressive phenotype in many cancers. Intrinsic T-cell immunity against ARG1-derived epitopes peripheral blood cancer patients healthy subjects has previously been demonstrated. To evaluate antitumor efficacy peptide vaccines as...
<p>Collected supplementary data file with figures and figure legends.</p>
<div>Abstract<p>Expression of the L-arginine catabolizing enzyme arginase 1 (ARG1) is a central immunosuppressive mechanism mediated by tumor-educated myeloid cells. Increased activity ARG1 promotes formation an microenvironment and leads to more aggressive phenotype in many cancers. Intrinsic T-cell immunity against ARG1-derived epitopes peripheral blood cancer patients healthy subjects has previously been demonstrated. To evaluate antitumor efficacy peptide vaccines as...
<p>Collected supplementary data file with figures and figure legends.</p>
<h3>Background</h3> IO112 is an immune modulatory cancer therapy under preclinical development to target arginase-1-expressing tumor cells and inhibitory myeloid cells, such as derived suppressor (MDSCs), associated macrophages (TAMs). Arginase-1 acts a metabolic regulator at the site by reducing availability of L-arginine infiltrating thus T cell functionality proliferation. Previously, we demonstrated that triggers activation spontaneous CD4+ CD8+ T-cell responses against arginase-1, found...