8 results on '"Ossendorp, Ferry"'
Search Results
2. A Restricted Role for FcγR in the Regulation of Adaptive Immunity
- Author
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Fransen, Marieke F, Benonisson, Hreinn, Van Maren, Wendy W, Sow, Heng Sheng, Breukel, Cor, Linssen, Margot M, Claassens, Jill WC, Brouwers, Conny, Van Der Kaa, Jos, Camps, Marcel, Kleinovink, Jan Willem, Vonk, Kelly K, Van Heiningen, Sandra, Klar, Ngaisah, Van Beek, Lianne, Van Harmelen, Vanessa, Daxinger, Lucia, Nandakumar, Kutty S, Holmdahl, Rikard, Coward, Chris, Lin, Qingshun, Hirose, Sachiko, Salvatori, Daniela, Van Hall, Thorbald, Van Kooten, Cees, Mastroeni, Piero, Ossendorp, Ferry, Verbeek, J Sjef, Benonisson, Hreinn [0000-0002-2974-2038], Linssen, Margot M [0000-0002-9157-1073], Kleinovink, Jan Willem [0000-0002-4198-2077], Nandakumar, Kutty S [0000-0001-7790-8197], Holmdahl, Rikard [0000-0002-4969-2576], van Hall, Thorbald [0000-0002-9115-558X], van Kooten, Cees [0000-0002-6257-0899], Mastroeni, Piero [0000-0003-3838-4962], Verbeek, J Sjef [0000-0003-0934-6924], and Apollo - University of Cambridge Repository
- Subjects
Biomedical ,Basic Science ,1107 Immunology ,1.1 Normal biological development and functioning ,bacteria ,2.1 Biological and endogenous factors ,Inflammatory and Immune System ,biochemical phenomena, metabolism, and nutrition - Abstract
By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcγR-knockout mice, it has been concluded that FcγRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcγRs (FcγRI/II/III/IV-/- mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effector pathways were impaired, adaptive immune responses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like FcγRIIb-deficient mice, FcγRI/II/III/IV-/- mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcγRs in the modulation of the adaptive immune response in vivo. We conclude that FcγRs are downstream IgG effector molecules with a restricted role in the ontogeny and maintenance of the immune system, as well as the regulation of adaptive immunity.
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- 2018
- Full Text
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3. Additional file 1: of Novel TLR2-binding adjuvant induces enhanced T cell responses and tumor eradication
- Author
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Zom, Gijs, Willems, Marian, Khan, Selina, Sluis, Tetje Van Der, Kleinovink, Jan, Camps, Marcel, Marel, Gijsbert Van Der, Filippov, Dmitri, Melief, Cornelis, and Ossendorp, Ferry
- Abstract
Figure S1. Activation of B3Z hybridoma after co-culture with D1 DCs loaded with 1uM of indicated compounds. Activation determined by spectrophotometry (OD 595 nm). WT BMDC: BMDCs derived from wildtype C57BL/6; TAPKO BMDC: BMDCs derived from TAP-deficient C57BL/6 mice; SIINFEKL: sequence of short ovalbumin-derived CTL epitope. Similar results were obtained in one additional experiment. Significance determined by unpaired t-test: **** p
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- 2018
- Full Text
- View/download PDF
4. Polymeric nanoparticles for co-delivery of synthetic long peptide antigen and poly IC as therapeutic cancer vaccine formulation
- Author
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Rahimian, Sima, Fransen, Marieke F., Kleinovink, Jan Willem, Christensen, Jonatan Riis, Amidi, Maryam, Hennink, Wim E., Ossendorp, Ferry, Sub Drug delivery, UIPS - Utrecht Institute for Pharmaceutical Sciences, Sub Drug targeting, Pharmaceutics, Sub Drug delivery, UIPS - Utrecht Institute for Pharmaceutical Sciences, Sub Drug targeting, and Pharmaceutics
- Subjects
Papillomavirus E7 Proteins ,medicine.medical_treatment ,Freund's Adjuvant ,Uterine Cervical Neoplasms ,Pharmaceutical Science ,Peptide ,Cervix Uteri ,CD8-Positive T-Lymphocytes ,Pharmacology ,Incomplete Freund's adjuvant (IFA) ,chemistry.chemical_compound ,Medicine ,Incomplete ,Glycolic acid ,chemistry.chemical_classification ,Human papillomavirus 16 ,education.field_of_study ,Vaccination ,virus diseases ,Poly IC ,Female ,Adjuvant ,pLHMGA ,Interferon Inducers ,Polyesters ,Molecular Sequence Data ,Population ,Cancer Vaccines ,Immune system ,Adjuvants, Immunologic ,Antigen ,Cell Line, Tumor ,Animals ,Humans ,Amino Acid Sequence ,education ,Human papillomavirus (HPV) ,business.industry ,Papillomavirus Infections ,TLR3 ligand ,Freund's djuvant (IFA) ,Virology ,Synthetic long peptide (SLP) ,Mice, Inbred C57BL ,Therapeutic cancer vaccine ,Poly I-C ,chemistry ,Nanoparticles ,Cancer vaccine ,business - Abstract
The aim of the current study was to develop a cancer vaccine formulation for treatment of human papillomavirus (HPV)-induced malignancies. Synthetic long peptides (SLPs) derived from HPV16 E6 and E7 oncoproteins have been used for therapeutic vaccination in clinical trials with promising results. In preclinical and clinical studies adjuvants based on mineral oils (such as incomplete Freund's adjuvant (IFA) and Montanide) are used to create a sustained release depot at the injection site. While the depot effect of mineral oils is important for induction of robust immune responses, their administration is accompanied with severe adverse and long lasting side effects. In order to develop an alternative for IFA family of adjuvants, polymeric nanoparticles (NPs) based on hydrophilic polyester (poly(d,l lactic-co-hydroxymethyl glycolic acid) (pLHMGA)) were prepared. These NPs were loaded with a synthetic long peptide (SLP) derived from HPV16 E7 oncoprotein and a toll like receptor 3 (TLR3) ligand (poly IC) by double emulsion solvent evaporation technique. The therapeutic efficacy of the nanoparticulate formulations was compared to that of HPV SLP + poly IC formulated in IFA. Encapsulation of HPV SLP antigen in NPs substantially enhanced the population of HPV-specific CD8+ T cells when combined with poly IC either co-encapsulated with the antigen or in its soluble form. The therapeutic efficacy of NPs containing poly IC in tumor eradication was equivalent to that of the IFA formulation. Importantly, administration of pLHMGA nanoparticles was not associated with adverse effects and therefore these biodegradable nanoparticles are excellent substitutes for IFA in cancer vaccines.
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- 2015
5. Effectiveness of slow-release systems in CD40 agonistic antibody immunotherapy of cancer
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Fransen, Marieke F., Cordfunke, Robert A., Sluijter, Marjolein, Van Steenbergen, Mies J., Drijfhout, Jan W., Ossendorp, Ferry, Hennink, Wim E., Melief, Cornelis J M, Sub Drug delivery, UIPS - Utrecht Institute for Pharmaceutical Sciences, Pharmaceutics, Sub Drug delivery, UIPS - Utrecht Institute for Pharmaceutical Sciences, and Pharmaceutics
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Slow-release ,Male ,medicine.drug_class ,medicine.medical_treatment ,T cell ,Cancer immunotherapy ,Oleic Acids ,Pharmacology ,Microparticles ,CD8-Positive T-Lymphocytes ,Monoclonal antibody ,Mice ,Montanide ISA-51 ,Immunology and Microbiology(all) ,medicine ,Side-effects ,Animals ,Mannitol ,CD40 Antigens ,Hybridomas ,General Veterinary ,General Immunology and Microbiology ,biology ,business.industry ,Environmental and Occupational Health ,Public Health, Environmental and Occupational Health ,Cancer ,Antibodies, Monoclonal ,Dextrans ,Immunotherapy ,Neoplasms, Experimental ,medicine.disease ,veterinary(all) ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Infectious Diseases ,Delayed-Action Preparations ,biology.protein ,Systemic administration ,Molecular Medicine ,Monoclonal antibodies ,Public Health ,Antibody ,business - Abstract
Slow-release delivery has great potential for specifically targeting immune-modulating agents into the tumor-draining area. In prior work we showed that local treatment of slowly delivered anti-CD40 antibody induced robust anti-tumor CD8+ T cell responses without systemic toxicity. We now report on the comparison of two slow-release delivery systems for their use in antibody-based immunotherapy of cancer. Anti-CD40 agonistic antibody delivered locally in mineral oil Montanide ISA 51 or in dextran-based microparticles activated tumor-specific T cell activation. Both slow-release formulations significantly decreased systemic side-effects compared to systemic administration of anti-CD40 antibody. However, dextran-based microparticles caused serious local inflammation associated with unwanted rapid outgrowth of tumors instead of the tumor clearance observed with delivery in Montanide. We therefore conclude that Montanide ISA 51 is to be preferred as a slow-release agent for CD40 agonist immunotherapy of cancer.
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- 2013
6. Additional file 1 of PD-L1 blockade engages tumor-infiltrating lymphocytes to co-express targetable activating and inhibitory receptors
- Author
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Beyrend, Guillaume, EsmĂŠ Van Der Gracht, Ayse Yilmaz, Duikeren, Suzanne Van, Camps, Marcel, HĂśllt, Thomas, Vilanova, Anna, Unen, Vincent Van, Koning, Frits, Miranda, Noel De, Arens, Ramon, and Ossendorp, Ferry
- Subjects
3. Good health - Abstract
Figure S1. Mass cytometry panel and marker expression. Figure S2. Quality control assessment of the data generated by mass cytometry. Figure S3. Identification of CD4+ and CD8+ TAI cells in the MCA205 sarcoma model. Figure S4. Synergy of combination immunotherapy. Table S1. FACS panels used in the study. (DOCX 2099 kb)
7. Additional file 1 of PD-L1 blockade engages tumor-infiltrating lymphocytes to co-express targetable activating and inhibitory receptors
- Author
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Beyrend, Guillaume, EsmĂŠ Van Der Gracht, Ayse Yilmaz, Duikeren, Suzanne Van, Camps, Marcel, HĂśllt, Thomas, Vilanova, Anna, Unen, Vincent Van, Koning, Frits, Miranda, Noel De, Arens, Ramon, and Ossendorp, Ferry
- Subjects
3. Good health - Abstract
Figure S1. Mass cytometry panel and marker expression. Figure S2. Quality control assessment of the data generated by mass cytometry. Figure S3. Identification of CD4+ and CD8+ TAI cells in the MCA205 sarcoma model. Figure S4. Synergy of combination immunotherapy. Table S1. FACS panels used in the study. (DOCX 2099 kb)
8. Autophagy regulates long-term cross-presentation by murine dendritic cells
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Ferry Ossendorp, Martijn Verdoes, Christian Münz, Nataschja I Ho, Marcel Camps, University of Zurich, and Ossendorp, Ferry
- Subjects
0301 basic medicine ,autophagy ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Antigen presentation ,Immunology ,Adaptive immunity ,610 Medicine & health ,Biology ,CD8-Positive T-Lymphocytes ,10263 Institute of Experimental Immunology ,DC ,Autophagy-Related Protein 5 ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Cross-Priming ,Antigen ,LC3 ,Immunology and Allergy ,Animals ,Basic ,Mice, Knockout ,2403 Immunology ,Antigen Presentation ,Microscopy, Confocal ,Autophagy ,Histocompatibility Antigens Class I ,Autophagosomes ,Cross-presentation ,Dendritic Cells ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,Proteasome ,cross‐presentation ,2723 Immunology and Allergy ,570 Life sciences ,biology ,Surface expression ,Research Article|Basic ,Wortmannin ,MHCI ,Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] ,Microtubule-Associated Proteins ,CD8 ,030215 immunology ,Research Article - Abstract
Autophagy has been reported to be involved in supporting antigen cross‐presentation by dendritic cells (DCs). We have shown that DCs have the ability to store antigen for a prolonged time in endolysosomal compartments and thereby sustain MHCI antigen cross‐presentation to CD8+ T cells. In the current study, we investigated the role of autophagy in long‐term antigen presentation. We show that the autophagy machinery has a negative impact on storage of antigen in DCs. Atg5–/–DCs which are deficient in autophagy or DCs treated with common autophagy inhibitors showed enhanced antigen storage and antigen cross‐presentation. This augmented antigen cross‐presentation effect is independent of altered proteasome enzyme activity or MHCI surface expression on DCs. We visualized that the storage compartments are in close proximity to LC3 positive autophagosomes. Our results indicate that autophagosomes disrupt antigen storage in DCs and thereby regulate long‐term MHCI cross‐presentation., Protein antigen‐antibody complexes are efficiently taken up by dendritic cells and conserved in storage compartments for prolonged antigen cross‐presentation to CD8+ T cells. LC3‐positive autophagosomes can breakdown antigen storage compartments thereby regulating the cross‐presentation capacity of dendritic cells.
- Published
- 2020
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