A5018521491- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Immune Response and Inflammation
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Cancer Immunotherapy and Biomarkers
- Transgenic Plants and Applications
- Inflammasome and immune disorders
- Influenza Virus Research Studies
- Cancer Research and Treatments
- CAR-T cell therapy research
- Pediatric health and respiratory diseases
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- Advanced biosensing and bioanalysis techniques
- Pneumonia and Respiratory Infections
National Institutes of Health
2025
Leiden University Medical Center
2018-2022
The murine MC-38 colorectal cancer model is a commonly used for with high mutational burden, which sensitive immune checkpoint immunotherapy. We set out to analyze endogenous CD8+ T cell responses neo-antigens in tumor-bearing mice and after anti-PD-L1 therapy. Through combination of whole-exome sequencing analysis mass spectrometry MHC class I eluted peptides we could identify eight candidate epitopes. Of these, neo-epitope encoded by point-mutation the sequence ribosomal protein L18...
The combination of immune-stimulating strategies has the potency to improve immunotherapy cancer. Vaccination against neoepitopes derived from patient tumor material can generate tumor-specific T cell immunity, which could reinforce efficacy checkpoint inhibitor therapies such as anti-PD-1 treatment. DNA vaccination is a versatile platform that allows inclusion multiple neoantigen-coding sequences in single formulation and therefore represents an ideal for neoantigen vaccination. We...
Pyroptosis is a recently discovered form of inflammatory programmed necrosis characterized by caspase-1-mediated and gasdermin D-dependent cell death leading to the release pro-inflammatory cytokines such as Interleukin-1 beta (IL-1β). Here, we evaluated whether pyroptosis could be exploited in DNA vaccination incorporating constitutively active variant caspase-1 antigen-expressing DNA. In vitro, transfection with induced pro-IL-1β maturation IL-1β well death. To test genetic adjuvant for...
Recent studies have shown a high potency of protein-based vaccines for cell-mediated cancer immunotherapy. However, due to their poor cellular uptake, efficient immune responses with soluble protein antigens are often not observed. As result superior nanogels loaded antigenic peptides were investigated in this study as carrier systems Different synthetic long (SLPs) containing the CTL and CD4+ T-helper (Help) epitopes synthesized covalently conjugated via disulfide bonds polymeric network...
Self-adjuvanting vaccines, wherein an antigenic peptide is covalently bound to immunostimulating agent, have been shown be promising tools for immunotherapy. Synthetic Toll-like receptor (TLR) ligands are ideal adjuvants covalent linking peptides or proteins. We here introduce a conjugation-ready TLR4 ligand, CRX-527, potent powerful lipid A analogue, in the generation of novel conjugate-vaccine modalities. Effective chemistry has developed synthesis ligand as well connection it antigen....
Peptide-based therapeutic immunizations represent safe approaches to elicit antigen-specific T cell responses, but their broad utility remains limited due poor immunogenicity and short in vivo stability rapid degradation clearance. Here we employed synthetic bacterial spore-like particles, "SSHELs", made entirely of biocompatible materials, deliver a model peptide antigen the absence additional adjuvants. SSHELs carrying were internalized by dendritic cells SSHEL-delivered peptides then...
MHC class II glycoproteins (MHC-II) bind peptides derived from exogenous antigens and dendritic cells (DCs) present these peptide MHC-II (pMHC-II) complexes to antigen-specific CD4 T during immune responses. The turnover of surface pMHC-II on antigen-presenting (APCs) is controlled by ubiquitin-mediated degradation the E3 ubiquitin ligase March-I. To study March-I protein expression, we have generated a mouse in which V5 epitope-tag was knocked-in endogenous gene, thereby allowing us follow...
Simultaneous triggering of Toll-like receptors (TLRs) and NOD-like (NLRs) has previously been shown to synergistically activate monocytes, dendritic cells, macrophages. We applied these properties in a T-cell vaccine setting by conjugating the NOD2-ligand muramyl-dipeptide (MDP) TLR2-ligand Pam3CSK4 synthetic peptide derived from model antigen. Stimulation human DCs with MDP-peptide-Pam3CSK4 conjugate led strongly increased secretion pro-inflammatory Th1-type cytokines chemokines. further...
Covalent linking of immunogenic oligopeptides with synthetic Toll-like receptor ligands is a useful approach to develop self-adjuvanting vaccines. In particular, small-molecule based agonists 7 (TLR7) that are derived from 8-oxo-adenine core potentially promising because these chemically robust TLR7 can be connected peptide T-cell epitopes via straightforward solid-phase synthesis. this contribution we present the synthesis Boc-protected 9-benzyl-2-alkoxy-8-oxo-adenine building block and its...
We report an approach to identify tumor-specific CD4+ T cell neo-epitopes of both mouse and human cancer cells by analysis major histocompatibility complex (MHC) class II-eluted natural peptides. MHC II-presented peptide sequences are identified introducing the II transactivator (CIITA) in tumor that were originally negative. CIITA expression facilitates cell-surface molecules appropriate peptide-loading machinery. Peptide elution purified subsequent mass spectrometry reveals oncoviral- as...
Adjuvants play a determinant role in cancer vaccination by optimally activating APCs and shaping the T cell response. Bacterial-derived lipid A is one of most potent immune-stimulators known, recognized via Toll-like receptor 4 (TLR4). In this study, we explore use synthetic, non-toxic, analog CRX-527 as an adjuvant for peptide vaccines. This well-defined was covalently conjugated to antigenic peptides strategy improve vaccine efficacy. We show that coupling TLR4 agonist antigens improves...
Abstract Mannose‐6‐phosphate (M6P) is recognized by the mannose‐6‐phosphate receptor and plays an important role in transport of cargo to endosomes, making it attractive tool improve endosomal trafficking vaccines. We describe herein assembly peptide antigen conjugates carrying clusters mannose‐6‐ C ‐phosphonates (M6Po). The M6Po's are stable M6P mimics that resistant cleavage phosphate group endogenous phosphatases. Two different strategies for incorporation M6Po conjugate have been...
Introduction Recent developments have shown that effectiveness of therapy with checkpoint-blocking antibodies correlates the expansion and invigoration neo-antigen specific T cells. Alongside, peptide-based vaccines targeting onco-viral antigens to be effective inducers cell responses related reduction HPV-induced pre-malignancies. This suggests vaccination neoantigens is a viable immunotherapeutic strategy. A major limitation for broad application vaccinations characterisation...
The essential role for CD4-specific helper neoepitopes has been clearly demonstrated, but straightforward identification remains a major hurdle. Recent years, it become possible to identify CD8-specific through massspectrometric analysis of tumor-derived MHC class I elutions. Here, we report an approach similarly tumorspecific CD4+ T cell epitopes both mouse and human cancer cells. II-presented peptide sequences were identified by introducing the II transactivator CIITA in tumor cells that...