A5040069297- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Phagocytosis and Immune Regulation
- Cancer Research and Treatments
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Immune cells in cancer
- Ultrasound and Hyperthermia Applications
- Glioma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Inhalation and Respiratory Drug Delivery
- Advanced biosensing and bioanalysis techniques
- Infectious Encephalopathies and Encephalitis
- Molecular Biology Techniques and Applications
- Cytomegalovirus and herpesvirus research
- Viral gastroenteritis research and epidemiology
- Adipokines, Inflammation, and Metabolic Diseases
Ghent University Hospital
2021-2024
Ghent University
2012-2024
Cancer Research Institute Ghent
2018-2024
VIB-UGent Center for Medical Biotechnology
2016-2023
Vlaams Instituut voor Biotechnologie
2015-2019
Vrije Universiteit Brussel
2010-2016
Bio-Medical Science (South Korea)
2014
Laboratoire de Chimie Moléculaire
2013
Queen Mary University of London
2012
The use of tumor-associated antigen (TAA) mRNA for therapeutic purposes is under active investigation. To be effective, vaccines need to deliver activation stimuli in addition TAAs dendritic cells (DC). In this study, we evaluated whether intranodal delivery TAA together with TriMix, a mix encoding CD40 ligand, constitutive Toll-like receptor 4 and CD70, results the situ modification maturation DCs, hence, priming TAA-specific T cells. We showed selective uptake translation vivo by lymph...
Abstract Localized therapeutic modalities that subvert the tumor microenvironment from immune‐suppressive to pro‐immunogenic can elicit systemic antitumor immune responses induce regression of directly treated as well nontreated distal tumors. A key toward generating robust T cell is activation dendritic cells (DCs) in microenvironment. Treatment with agonists triggering various pattern recognition receptors very efficient activate DCs, yet suffers induction serious immune‐related adverse...
ABSTRACT Lentiviral vectors are promising vaccine vector candidates that have been tested extensively in preclinical models of infectious disease and cancer immunotherapy. They also used gene therapy clinical trials both for the ex vivo modification cells direct injection. It is therefore critical to understand mechanism(s) by which such might stimulate immune system. We evaluated effect lentiviral on myeloid dendritic (DC), main target transduction following subcutaneous immunization. The...
Abstract Modulating the activity of tumor-infiltrating dendritic cells (TiDC) provides opportunities for novel cancer interventions. In this article, we report on our study uptake mRNA by CD8α+ cross-presenting TiDCs upon its intratumoral (i.t.) delivery. We exploited property to deliver encoding costimulatory molecule CD70, activation stimuli CD40 ligand, and constitutively active Toll-like receptor 4, referred as TriMix mRNA. show that are reprogrammed mature antigen-presenting migrate...
Cancer immunotherapy can induce durable antitumor responses. However, many patients poorly respond to such therapies. Here we describe a generic therapy that is based on the intratumor delivery of mRNA codes for necroptosis executioner mixed lineage kinase domain-like (MLKL) protein. This intervention stalls primary tumor growth and protects against distal disseminated formation in syngeneic mouse melanoma colon carcinoma models. Moreover, MLKL-mRNA treatment combined with immune checkpoint...
Given their high potential to evoke cytolytic T cell responses, tumor antigen-encoding messenger RNA (mRNA) vaccines are now being intensively explored as therapeutic cancer vaccines. mRNA clearly benefit from wrapping the into nano-sized carriers such lipoplexes that protect degradation and increase its uptake by dendritic cells in vivo. Nevertheless, early innate host factors regulate induction of lipoplex have remained unresolved. Here, we demonstrate induce a potent type I interferon...
Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial which dendritic (DC) vaccine targeting patient-individual neoantigens evaluated patients with resected NSCLC. Vaccine manufacturing feasible six 10 enrolled patients. Toxicity limited to grade 1-2 adverse events. Systemic T responses are observed five out vaccinated patients, remaining detectable up 19 months post vaccination....
An ideal generic cancer immunotherapy should mobilize the immune system to destroy tumor cells without harming healthy and remain active in case of recurrence. Furthermore, it preferably not rely on tumor-specific surface markers, as these are only available a limited set malignancies. Despite approval for treatment various cancers, clinical application cytokines is still impeded by their multiple toxic side effects. Type I IFN has long history cancer, but its multifaceted activity pattern...
Although the main site of action for myeloid-derived suppressor cells (MDSCs) is most likely tumor microenvironment, so far study these has been largely restricted to spleen-derived MDSCs. In this study, we compared suppressive capacity splenic and tumor-derived MDSCs in different subcutaneous mouse models. We investigated which mechanisms were involved. Finally, whether regulatory T (Treg ) cooperate suppression T-cell responses. all models, granulocytic (grMDSC) strongly suppress CD4(+)...
Despite approval for the treatment of various malignancies, clinical application cytokines such as type I interferon (IFN) is severely impeded by their systemic toxicity. AcTakines (Activity-on-Target cytokines) are optimized immunocytokines that, when injected in mice, only reveal activity upon cell-specific impact. We here show that IFN-derived AcTaferon targeted to tumor displays strong antitumor without any associated toxicity, contrast with wild IFN. Treatment CD20-targeted CD20+...
mRNA-lipoplex vaccines are currently being explored in phase II clinical trials for the treatment of patients with advanced solid tumors. Mechanistically, these characterized by induction type I interferon (IFN) centered innate responses. Earlier studies have identified IFNs as major regulators T cell response instigated vaccines. However, stimulatory or, contrast, profound inhibitory effects were described depending on study. In this mouse study, we demonstrated that opposing roles IFN...
Article8 January 2020Open Access Source DataTransparent process Safe eradication of large established tumors using neovasculature-targeted tumor necrosis factor-based therapies Leander Huyghe Cytokine Receptor Laboratory, VIB Center for Medical Biotechnology, Department Biomolecular Medicine, Ghent University, Ghent, Belgium Search more papers by this author Alexander Van Parys BelgiumShared authorship Anje Cauwels Sandra Lint Stijn De Munter Clinical Chemistry, Microbiology and Immunology,...
Tumor antigen-encoding mRNA for dendritic cell (DC)-based vaccination has gained increasing popularity in recent years. Within this context, two main strategies have entered the clinical trial stage: use of ex vivo antigen loading DCs and direct application as a source vivo. transfected with mRNA-encoding Wilms' tumor 1 (WT1) protein shown promising results. Using stepwise approach, we re-engineered WT1 cDNA-carrying transcription vector to improve translational characteristics...
Molecular mimetics of the caspase activator second mitochondria-derived (SMAC) are being investigated for use in cancer therapy, but an understanding vivo effects remains incomplete. In this study, we offer evidence that SMAC elicit a proinflammatory cell death cells engages adaptive antitumor immune response. Cancer different histologic origin underwent apoptosis when transduced with lentiviral vectors encoding cytosolic form mimetic LV-tSMAC. Strikingly, treatment tumor-bearing mice...
To increase the safety and possibly efficacy of HIV-1 derived lentivectors (LVs) as an anti-cancer vaccine, we recently developed Nanobody (Nb) display technology to target LVs antigen presenting cells (APCs). In this study, extend these data with exclusive targeting conventional dendritic (DCs), which are believed be main cross-presenting APCs for induction a TH1-conducted antitumor immune response. The immunogenicity DC-subtype targeted was compared that broad tropism, general APC-targeted...
Annual administration and reformulation of influenza vaccines is required for protection against seasonal infections. However, the induction strong long-lasting T cells critical to reach broad potentially lifelong antiviral immunity. The NLRP3 inflammasome its product interleukin-1β (IL-1β) are pivotal mediators cellular immune responses influenza, yet, overactivation these systems leads side effects, which hamper clinical applications. Here, we present a bypass around toxicities by...