A5046458252- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Endometrial and Cervical Cancer Treatments
- Cervical Cancer and HPV Research
- Toxin Mechanisms and Immunotoxins
- T-cell and B-cell Immunology
- Immune responses and vaccinations
- Cancer Mechanisms and Therapy
- Genomics, phytochemicals, and oxidative stress
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- Immune Cell Function and Interaction
- Curcumin's Biomedical Applications
- Computational Drug Discovery Methods
- Renal and related cancers
- Colorectal Cancer Screening and Detection
- Pharmacogenetics and Drug Metabolism
- Cutaneous Melanoma Detection and Management
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Research and Treatments
- Virus-based gene therapy research
- Microbial Inactivation Methods
Anticancer Fund
2015-2024
Vrije Universiteit Brussel
2008-2014
Universitair Ziekenhuis Brussel
2011
The effectiveness of the dendritic cell (DC) vaccination protocols that are currently in use could be improved by providing DCs with a more potent maturation signal. We therefore investigated whether T-cell stimulatory capacity human monocyte-derived increased co-electroporation different combinations CD40L, CD70, and constitutively active toll-like receptor 4 (caTLR4) encoding mRNA. show immature electroporated CD40L and/or caTLR4 mRNA, but not those CD70 acquire mature phenotype along an...
A critical factor determining the effectiveness of currently used dendritic cell (DC)-based vaccines is DC activation or maturation status. We have recently shown that T-cell stimulatory capacity DCs pulsed with tumor-antigen-derived peptides can be considerably increased by activating through electroporation mRNA encoding CD40 ligand, CD70, and a constitutively active Toll-like receptor 4 (TriMix DCs). Here, we investigate whether TriMix coelectroporated whole tumor-antigen-encoding...
The immunostimulatory capacity of dendritic cells is improved by co-electroporation with mRNA encoding CD40 ligand, constitutively active toll-like receptor 4, and CD70 (TriMix-DC). This pilot clinical trial evaluated the feasibility, safety, immunogenicity a therapeutic vaccination containing autologous TriMix-DC co-electroporated human leukocyte antigen class II-targeting signal linked to 1 4 melanoma-associated antigens (MAGE-A3, MAGE-C2, tyrosinase, gp100) in patients advanced melanoma....
Repurposing is a drug development strategy that seeks to use existing medications for new indications. In oncology, there an increased level of activity looking at the non-cancer drugs as possible cancer treatments. The Drugs in Oncology (ReDO) project has used literature-based approach identify licensed with published evidence anticancer activity. Data from 268 have been included database (ReDO_DB) developed by ReDO project. Summary results are outlined and assessment clinical trial also...
Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL) stimulates T-cell responses against the presented tumor-associated antigens (TAAs). In current clinical trials, systemic metastases are treated, requiring priming and/or expansion preexisting TAA-specific T that able to migrate both skin and internal organs. We monitored presence CD8 + infiltrating at sites intradermal TriMixDC-MEL injection (SKILs) within circulation treated in two trials. 10 out fourteen...
It is generally thought that dendritic cells (DCs) loaded with full-length tumor antigen could improve immunotherapy by stimulating broad T-cell responses and allowing treatment irrespective of the patient's human leukocyte (HLA) type. To investigate this, we determined specificity T from melanoma patients treated DCs mRNA encoding a fused to signal peptide an HLA class II sorting signal, presentation in I II. In delayed-type hypersensitive (DTH)-biopsies blood, found functional CD8(+)...
Clarithromycin (CAM) is a well-known macrolide antibiotic available as generic drug. CAM traditionally used for many types of bacterial infections, treatment Lyme disease and eradication gastric infection with Helicobacter pylori. Extensive preclinical clinical data demonstrate potential role to treat various tumours in combination conventional treatment. The mechanisms action underlying the anti-tumour activity are multiple include prolonged reduction pro-inflammatory cytokines, autophagy...
A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one the tumor lesions irradiated (8Gyx3) on days 15, 17, 19. The primary endpoint objective response rate...
Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade cancers showed objective responses 13-17% of patients. This could be due to immunosuppressive effects exerted by tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint with radiation delivers benefit that is believed abscopal effect. Addition immune modulation agents has also shown enhance...
Abstract Regulatory T cells (Tregs) counteract anticancer immune responses through a number of mechanisms, limiting dendritic cell (DC)–based immunotherapy. In this study, we investigated the influence various DC activation stimuli on Treg functionality. We compared DCs activated by electroporation with mRNA encoding constitutively active TLR4 (caTLR4) and CD40 ligand (DiMix-DCs), or these factors together costimulatory molecule CD70 (TriMix-DCs) maturated in presence mixture inflammatory...
Curcumin is a botanical with anti-tumor and immunomodulatory properties. We hypothesized that curcumin supplementation might influence inflammatory biomarker levels in endometrial carcinoma (EC). In this open-label, non-randomized phase 2 study (NCT02017353), seven EC patients consumed g/day Phytosome (CP) orally for weeks. Blood was taken at baseline, days 1, 7, 14, 21. The following analytes were measured: curcuminoids metabolites, 56 biomarkers, COX-2, frequencies of myeloid-derived...
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...
A decade of collective work by tumor immunologists has led to improved large scale generation, maturation, antigen loading and administration dendritic cells (DCs) cancer patients, promoting enhanced antitumor activity. We alleviated the HLA-restriction in DC therapy demonstrated that it is meaningful treat patients with DCs irrespective their HLA type.
2519 Background: Autologous monocyte derived dendritic cells (DC) electroporated with synthetic messenger RNA (smRNA) encoding CD40 ligand, a constitutively active TLR4, and CD70 (TriMixDC), together smRNA fusion-proteins of HLA-class II targeting signal melanoma associated antigen are immunogenic when administered ID (Wilgenhof et al. ASCO AM 2009). The TriMixIDIV clinical trial investigates the safety, immunogenicity, activity combined IV administration in patients pretreated melanoma....
Metastatic melanoma runs a predictable detrimental course in the vast majority of patients. New modalities immunotherapy, such as antigen-specific therapeutic vaccination and cytotoxic T-lymphocyte antigen 4 (CTLA-4) receptor blockade by monoclonal antibodies (mAbs), have been associated with atypical kinetics tumor response that differ from those observed during treatment. Recently, new criteria proposed based on characteristics clinical studies ipilimumab (the so-called ‘immune-related...
Melanoma metastases are characterized by pronounced neo-angiogenesis and spontaneous bleeding frequently occurring within central nervous system metastases. Clinically apparent hemorrhage subcutaneous melanoma metastases, however, is a rare event that coincides with progression of such We report, to our knowledge the first observation, on regression overlying skin in three patients stage IV who participated clinical trials therapeutic vaccination. In two patients, loss arterial flow Doppler...
2507 Background: Autologous monocyte-derived DC electroporated with synthetic mRNA encoding CD40 ligand, a constitutively active TLR4, and CD70 (TriMix-DC) have superior T-cell stimulatory capacity. In pilot clinical trial, ID administration of TriMixDC-MEL (a mixture TriMix-DC co-electroporated fusion DC.LAMP 1 4 melanoma associated antigens) was immunogenic but resulted in limited anti-tumor activity patients (pts) advanced melanoma. Ipilimumab (IPI) is CTLA-4 blocking mAb established pts...