A5090318866- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HER2/EGFR in Cancer Research
- Photodynamic Therapy Research Studies
- Nanoplatforms for cancer theranostics
- Immune cells in cancer
- Cancer Cells and Metastasis
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- bioluminescence and chemiluminescence research
- Lung Cancer Treatments and Mutations
- Cancer Research and Treatments
- Lung Cancer Research Studies
- Glycosylation and Glycoproteins Research
- vaccines and immunoinformatics approaches
- Lung Cancer Diagnosis and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Pancreatic and Hepatic Oncology Research
- Esophageal Cancer Research and Treatment
- Advanced Drug Delivery Systems
- Biosimilars and Bioanalytical Methods
Cancer Center Amsterdam
2020-2024
Oncode Institute
2022-2024
Vrije Universiteit Amsterdam
2021-2024
Amsterdam University Medical Centers
2020-2024
Leiden University Medical Center
2012-2023
Amsterdam Institute for Addiction Research
2023
Dutch Cancer Society
2023
Amsterdam UMC Location Vrije Universiteit Amsterdam
2020-2021
Leiden University
2019-2020
Dutch Blood Transfusion Society
2005-2015
PD-L1/PD-1 blocking antibodies have demonstrated therapeutic efficacy across a range of human cancers. Extending this benefit to greater number patients, however, will require better understanding how these therapies instigate anticancer immunity. Although the axis is typically associated with T cell function, we demonstrate here that dendritic cells (DCs) are an important target PD-L1 antibody. binds two receptors, PD-1 and B7.1 (CD80). expressed much more abundantly than on peripheral...
PD-1/PD-L1 checkpoint therapy for cancer is commonly considered to act by reactivating T cells in the tumor microenvironment. Here, we present data from 2 mouse models demonstrating an essential involvement of tumor-draining lymph nodes PD-1 and PD-L1 therapeutic efficacy. Immune activation induced treatment was predominantly observed tumor-draining, but not nondraining, reflected local accumulation CD8+ cells. Surgical resection these nodes, contralateral abolished therapy-induced...
Adequate spontaneous activation of tumor-specific T lymphocytes in tumor-bearing hosts is rare, despite the expression tumor antigens that are potentially highly immunogenic. For example, failure immune system to raise competent responses against established tumors expressing human adenovirus E1A-antigen allows this grow immunocompetent mice. We show systemic vivo administration agonistic anti-CD40 antibodies into mice results eradication mediated by CD8 + cells. Treatment resulted a strong...
Abstract Purpose: Blockade of CTLA-4 by antibodies has potentiated antitumor T-cell responses in both preclinical models and clinical trials. However, treatment with blocking is associated autoimmune inflammatory side effects. In this study, we propose a novel administration method for as monotherapy. Experimental Design: We use different mouse cancer to investigate the local antibody its effect on progression response. Results: By injecting subcutaneous slow-release delivery formulation...
Immunotherapy against tumors with anti-CD40 agonistic antibodies has been extensively studied in preclinical animal models and recently also clinical trials. Although promising results have obtained, antibody (Ab)-related toxicity a limiting factor. We reasoned that strict local activation of tumor-specific CD8 T cells through stimulation CD40 on the dendritic (DC) tumor area while excluding systemic might be sufficient for effective eradication can limit toxicity.Preclinical vivo...
Immunotherapy with PD-1/PD-L1-blocking antibodies is clinically effective for several tumor types, but the mechanism not fully understood. PD-L1 expression on biopsies generally regarded as an inclusion criterion this cancer therapy. Here, we describe PD-L1-blocking therapeutic responses of preclinical tumors in which was removed from cells, immune infiltrate. Lack malignant cells delayed outgrowth a CD8+ T cell-mediated fashion, showing importance molecule suppression. evident...
Abstract Photodynamic therapy (PDT) is a clinically applied tumor ablation method that reduces burden and may induce T-cell responses, providing therapeutic option for mutated tumors. In this study, we PDT in two mouse models assessed its effect on outgrowth of PDT-treated distant untreated established tumors resulted complete eradication most mice, which were then protected against rechallenge. Correspondingly, the was abrogated upon systemic depletion CD8+ T cells, indicating PDT-induced...
The efficacy of immunotherapy against advanced cancer may be improved by combination strategies. Photodynamic therapy (PDT) is a local tumor ablation method based on localized activation photosensitizer, leading to oxygen radical-induced cell death. PDT can enhance antitumor immune responses release antigen and danger signals, supporting protocols with immunotherapy.We investigated the systemic effects after treatment established tumors. In two independent aggressive mouse models, TC-1 RMA,...
IntroductionImmune checkpoint inhibitors (ICI), such as anti-PD-1 agents, have become part of the standard care treatment advanced non-small cell lung cancer (NSCLC). Predictive biomarkers are needed to identify patients that benefit from treatments. Tumor infiltrating lymphocytes (TILs) and PD-L1 major players in ICI mechanism action. In this study, we assess impact real-world clinicopathological variables, including TILs PD-L1, on efficacy.MethodsWe performed a monocenter retrospective...
Immune checkpoint inhibitors have revolutionized cancer therapy, yet the efficacy of these treatments is often limited by heterogeneous and hypoxic tumor microenvironment (TME) solid tumors. In TME, programmed death-ligand 1 (PD-L1) expression on cells mainly regulated Interferon-gamma (IFN-γ), which induces T cell exhaustion enables immune evasion. this study, we demonstrate that acidosis, a common characteristic tumors, significantly increases IFN-γ-induced PD-L1 aggressive cells, thus...
Cell-free DNA (cfDNA) can be isolated and sequenced from blood and/or urine of cancer patients. Conventional short-read sequencing lacks deployability speed biased for short cfDNA fragments. Here, we demonstrate that with Oxford Nanopore Technologies (ONT) achieve delivery genomic fragmentomic data liquid biopsies. Copy number aberrations fragmentation patterns determined in less than 24 h sample collection. The tumor-derived fraction calculated plasma lung patients bladder was highly...
Vγ9Vδ2 T cells are effector with proven antitumor efficacy against a broad range of cancers. This study aimed to assess the activity and safety bispecific antibody directing EGFR-expressing tumors. An EGFR-Vδ2 T-cell engager (bsTCE) was generated, its capacity activate trigger tested in multiple vitro, vivo, ex vivo models. Studies explore were conducted using cross-reactive surrogate engagers nonhuman primates (NHP). We found that from peripheral blood tumor specimens patients EGFR+ cancers...
Abstract The fate of naive CD8+ T cells is determined by the environment in which they encounter MHC class I presented peptide Ags. manner tumor Ags are a longstanding matter debate. Ag presentation might be mediated draining lymph nodes or via cross-presentation professional APC. Either pathway insufficient to elicit protective antitumor immunity. We now demonstrate using syngeneic mouse model, expressing an derived from early region 1A human adenovirus type 5, that inadequate nature CTL...
Abstract CD8+ T cells have the potential to attack and eradicate cancer cells. The efficacy of therapeutic vaccines against cancer, however, lacks defined immune correlates tumor eradication after (therapeutic) vaccination based on features Ag-specific cell responses. In this study, we examined responses elicited by various peptide TLR agonist-based vaccine formulations in nontumor settings show that formation CD62L−KLRG1+ effector-memory producing effector cytokines IFN-γ TNF predicts...
Targeting of antigens to dendritic cells (DCs) induce strong cellular immune response can be established by loading in a nano‐sized carrier and keeping the antigen associated with particles until they are internalized DCs. In present study, model (ovalbumin, OVA) is immobilized cationic dextran nanogels via disulfide bonds. These bonds stable extracellular environment but reduced cytosol DCs due presence glutathione. Reversible immobilization OVA demonstrated fact that hardly any release...
Thermosensitive poloxamer 407 (P407) hydrogels were evaluated as slow release system for optimizing CTLA-4 therapy. Slow reduces systemic antibody levels and potentially mitigates the side effects of The 25% P407 hydrogel is injectable at room temperature depots are established quickly after subcutaneous injection. Scanning electron microscopy revealed porous structure hydrogel, average pore surface was 1335 μm2. Release studies optimized using human IgG antibody. easily incorporated in by...
Preclinical studies show that locoregional CTLA-4 blockade is equally effective in inducing tumor eradication as systemic delivery, without the added risk of immune-related side effects. This efficacy related to access blocking antibodies tumor-draining lymph nodes (TDLNs). Local delivery anti-CTLA-4 after surgical removal primary melanoma, before sentinel node biopsy (SLNB), provides a unique setting clinically assess role TDLN biological blockade. Here, we have evaluated safety,...
The structure of cell-free DNA (cfDNA) is altered in the blood patients with cancer. From whole-genome sequencing, we retrieve cfDNA fragment-end composition using a new software (FrEIA [fragment end integrated analysis]), as well size and tumor fraction three independent cohorts (n = 925 cancer from >10 types 321 control samples). At 95% specificity, detect 72% samples at least one measure, including 64% early-stage 220). detection correlates shorter overall (p 0.0086) recurrence-free...
In advanced-stage NSCLC, tumor proportion score (TPS) is typically used to predict the efficacy of immune checkpoint inhibitors (ICIs). Nevertheless, in other cancer types, combined positive (CPS), which covers programmed death-ligand 1 (PD-L1) expression on both and surrounding cells, used. We investigated predictive value CPS comparison TPS advanced NSCLC.A monocenter, retrospective study was performed patients with NSCLC treated ICI monotherapy between 2015 2021. Hematoxylin eosin PD-L1...
The aim of the present study was to improve immunogenicity peptide epitope vaccines using novel nanocarriers based on self-assembling materials. Several studies demonstrated that antigens in nanoparticulate form induce stronger immune responses than their soluble forms. However, several issues such as poor loading and risk inducing T cell anergy due premature release antigenic epitopes have challenged clinical success systems. In study, we developed two vaccine delivery systems by appending...