A5002745380- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Cutaneous Melanoma Detection and Management
- Ocular Oncology and Treatments
- Melanoma and MAPK Pathways
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Multiple Myeloma Research and Treatments
- Colorectal Cancer Treatments and Studies
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Monoclonal and Polyclonal Antibodies Research
- Nanoplatforms for cancer theranostics
- Health Systems, Economic Evaluations, Quality of Life
- Cell Image Analysis Techniques
- Image Processing Techniques and Applications
- Biomedical Ethics and Regulation
- Corneal Surgery and Treatments
- Radiopharmaceutical Chemistry and Applications
- Ethics in Clinical Research
- melanin and skin pigmentation
- Vascular Tumors and Angiosarcomas
Radboud University Medical Center
2016-2025
Radboud University Nijmegen
2016-2025
Copenhagen University Hospital
2019-2025
University Hospital and Clinics
2024
University Medical Center
2015-2024
Radboud Institute for Molecular Life Sciences
2013-2022
Herlev Hospital
2019-2020
Bipar
2016
Data Harbor (United States)
2015
Colorado Department of Public Health and Environment
2014
Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocyte-derived DCs, which require extensive vitro manipulation. Here, we report a clinical study exploiting primary CD1c(+) myeloid naturally circulating the blood.Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous activated by only brief (16 hours) ex vivo culture and loaded with tumor-associated antigens tyrosinase...
Dendritic cell (DC)-based vaccination for cancer treatment has seen considerable development over recent decades. However, this field is currently in a state of flux toward niche-applications, owing to paradigm-shifts immuno-oncology mobilized by T cell-targeting immunotherapies. DC vaccines are typically generated using autologous (patient-derived) DCs exposed tumor-associated or -specific antigens (TAAs TSAs), the presence immunostimulatory molecules induce maturation, followed reinfusion...
The brain is a specialized immune site representing unique tumor microenvironment. availability of fresh material for ex vivo analysis often limited because large parts many tumors are resected using ultrasonic aspiration. We analyzed aspirates as biosource to study suppressive mechanisms in 83 human tumors. Lymphocyte infiltrates tissues and were comparable with respect lymphocyte content viability. Applying aspirates, we detected massive infiltration CD4+FoxP3+CD25high CD127low regulatory...
To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part effective anticancer immunotherapy, we investigated immunologic and clinical responses to vaccination with dendritic (DC) pulsed either MHC class I (MHC-I)-restricted epitopes alone or both II (MHC-I/II)-restricted epitopes. We enrolled 33 stage III IV HLA-A*02:01-positive patients melanoma in this study, whom 29 were evaluable for response. Patients received intranodal vaccinations cytokine-matured DCs...
Tumor immunosurveillance plays a major role in melanoma, prompting the development of immunotherapy strategies. The gut microbiota composition, influencing peripheral and tumoral immune tonus, earned its credentials among predictors survival melanoma. MIND-DC phase III trial (NCT02993315) randomized (2:1 ratio) 148 patients with stage IIIB/C melanoma to adjuvant treatment autologous natural dendritic cell (nDC) or placebo (PL). Overall, 144 collected serum stool samples before after 2...
Abstract Autologous natural dendritic cells (nDCs) treatment can induce tumor-specific immune responses and clinical in cancer patients. In this phase III trial (NCT02993315), 148 patients with resected stage IIIB/C melanoma were randomized to adjuvant nDCs ( n = 99) or placebo 49). Active consisted of intranodally injected autologous CD1c+ conventional plasmacytoid DCs loaded tumor antigens. The primary endpoint was the 2-year recurrence-free survival (RFS) rate, whereas secondary endpoints...
Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) has multiple advantages compared to peptide loading. We investigated the immunologic and clinical responses vaccination mRNA-electroporated DC in stage III IV melanoma patients.Twenty-six HLA*02:01 patients scheduled for radical lymph node dissection (stage III) 19 irresectable locoregional or distant metastatic disease (referred as IV) were included. Monocyte-derived DC, electroporated gp100...
PurposeTo assess the safety and efficacy of dendritic cell vaccination in metastatic uveal melanoma.DesignInterventional case series.MethodsWe analyzed 14 patients with melanoma treated vaccination. Patients received at least 3 vaccinations autologous cells, professional antigen-presenting cells loaded antigens gp100 tyrosinase. The main outcome measures were safety, immunologic response, overall survival.ResultsTumor-specific immune responses induced 4 (29%) patients. Dendritic...
Melanoma patients with regional metastatic disease are at high risk for recurrence and disease, despite radical lymph node dissection (RLND). We investigated the immunologic response clinical outcome to adjuvant dendritic cell (DC) vaccination in melanoma who underwent RLND curative intent. In this retrospective study, 78 metastasis received autologous DCs loaded gp100 tyrosinase were analyzed functional tumor-specific T responses skin-test infiltrating lymphocytes. The study shows that DC...
Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured pro-inflammatory cytokines and prostaglandin E2. We studied the safety efficacy of vaccination monocyte-derived a cocktail prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) E2 (VAC-DC). Stage III IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous (16 VAC-DC loaded keyhole...
Abstract Background Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination. Methods This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations gp100 tyrosinase mRNA-loaded monocyte-derived DCs with or without...
The majority of neoantigens arise from unique mutations that are not shared between individual patients, making neoantigen-directed immunotherapy a fully personalized treatment approach. Novel technical advances in next-generation sequencing tumor samples and artificial intelligence (AI) allow fast systematic prediction neoantigens. This study investigates feasibility, safety, immunity, anti-tumor potential the peptide-based neoantigen vaccine, EVX-01, including novel CD8+ T-cell inducing...
Background Neoantigens can serve as targets for T cell-mediated antitumor immunity via personalized neopeptide vaccines. Interim data from our clinical study NCT03715985 showed that the peptide-based neoantigen vaccine EVX-01, formulated in liposomal adjuvant, CAF09b, was safe and able to elicit EVX-01-specific cell responses patients with metastatic melanoma. Here, we present results dose-escalation part of study, evaluating feasibility, safety, efficacy, immunogenicity EVX-01 addition...
Autologous dendritic cell (DC) therapy is an experimental cellular immunotherapy that safe and immunogenic in patients with advanced melanoma. In attempt to further improve the therapeutic responses, we treated 15 melanoma, autologous monocyte-derived immature DC electroporated mRNA encoding CD40 ligand (CD40L), CD70 a constitutively active TLR4 (caTLR4) together tumor-associated antigen (TAA; respectively gp100 or tyrosinase). addition, were pulsed keyhole limpet hemocyanin (KLH) served as...
The identification of responding patients early during treatment would improve the capability to develop effective new immunotherapies more rapidly. Here, we describe a bioassay that may link T-cell-mediated immune responses later clinical benefits. This rests upon tenet immunotherapy tumor-specific effector T cells capable invading peripheral tissue can recognize tumor antigens and exert cytotoxic functions there. To show its utility, conducted retrospective study large cohort metastatic...
Uveal melanoma (UM) is the most common intraocular malignancy in adults and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed patients UM, we analyzed real-world outcomes nationwide population-based study. Clinical data UM were extracted from Danish Metastatic Melanoma database, database containing unselected records diagnosed Denmark. Survival before (pre-ICI, n = 32) after (post-ICI, 94) approval first-line...
Plasmacytoid dendritic cells (pDCs) and type 2 conventional (cDC2s) are currently under evaluation for use in cancer vaccines. Although both DC subsets can activate adaptive innate lymphocytes, their capacity to recruit such is rarely considered. Here, we show that pDCs cDC2s display a striking difference chemokine secretion, which correlates with the recruitment of distinct types immune effector cells. Activated express high levels CXCR3 ligands attract more CD8+ T cells, CD56+ γδ vitro,...
Background Immune checkpoint inhibitors (ICI) can lead to long-term responses in patients with metastatic melanoma. Still many melanoma are intrinsically resistant or acquire secondary resistance. Previous studies have used primary tumor tissue for biomarker assessment. Especially melanoma, lesions often present at different anatomical sites such as skin, lymph nodes, and visceral organs. The site may directly affect the microenvironment (TME). To evaluate impact of evolution on TME ICI...
Tumor-infiltrating lymphocytes appear to be a predictor of survival in many cancers, including cutaneous melanoma. We applied automated multispectral imaging determine whether density and distribution T cells within primary melanoma tissue correlate with metastatic patients after dendritic cell (DC) vaccination. CD3(+) infiltration tumors from 77 was quantified using the ratio intratumoral versus peritumoral T-cell densities (I/P ratio). Patients longer DC vaccination had stronger than...
The purpose of this study was to determine the toxicity profile dendritic cell (DC) vaccination in stage III and IV melanoma patients, evaluate whether there is a correlation between side effects immunologic clinical outcome. This retrospective analysis 82 137 vaccinated with monocyte-derived or naturally circulating autologous DCs loaded tumor-associated antigens gp100 tyrosinase. Median follow-up time 54.3 months patients 12.9 patients. Treatment-related adverse events occurred 84%...