Immunological dynamics after subcutaneous immunization with a squalene‐based oil‐in‐water adjuvant

Schetters, Sjoerd; Kruijssen, Laura; Crommentuijn, Matheus H.W.; Kalay, Hakan; Haan, Joke M. M. den; Kooyk, Yvette van

doi:10.1096/fj.202000848r

Cited by 15 publications

(15 citation statements)

References 52 publications

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“…Importantly, alum-based and oil-in-water adjuvants are usually used to induce humoralrather than cell-mediated immunity and we did not assess the humoral immune response in our study. Notably, Addavax has been shown to also trigger antigen-specific T cells 25 and we did observe a modest but insignificant boosting effect using this adjuvant. Since the anti-Mut immunization must be directed against the mutated epitopes only in order to prevent the development of auto-immunity, the use of peptides is ideally suited for personalized vaccination.…”

Section: Discussionmentioning

confidence: 49%

Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination

et al. 2021

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By conferring systemic protection and durable benefits, cancer immunotherapies are emerging as long-term solutions for cancer treatment. One such approach that is currently undergoing clinical testing is a therapeutic anti-cancer vaccine that uses two different viruses expressing the same tumor antigen to prime and boost anti-tumor immunity. By providing the additional advantage of directly killing cancer cells, oncolytic viruses (OVs) constitute ideal platforms for such treatment strategy. However, given that the targeted tumor antigen is encoded into the viral genomes, its production requires robust infection and therefore, the vaccination efficiency partially depends on the unpredictable and highly variable intrinsic sensitivity of each tumor to OV infection. In this study, we demonstrate that anti-cancer vaccination using OVs (Adenovirus (Ad), Maraba virus (MRB), Vesicular stomatitis virus (VSV) and Vaccinia virus (VV)) co-administered with antigenic peptides is as efficient as antigen-engineered OVs and does not depend on viral replication. Our strategy is particularly attractive for personalized anti-cancer vaccines targeting patient-specific mutations. We suggest that the use of OVs as adjuvant platforms for therapeutic anti-cancer vaccination warrants testing for cancer treatment.

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Section: Discussionmentioning

confidence: 49%

Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination

et al. 2021

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“…Also, pairing of C16:0 peptides with adjuvants that recruit moDCs to the site of injection such as AddaVax could be an interesting strategy. 46 Using different inhibitors, we demonstrate that the processing of C16:0 peptides follows a different route from that of unmodified peptides. Clearly, processing of C16:0 peptides relied on proteasomal degradation in the cytosol, endosomal acidification, and vacuolar processing via cathepsin S. In our hands, BFA did not affect the processing of the C16:0 gp100 peptides for presentation to CD8 + T cells, suggesting that loading of C16:0 gp100 on MHC class I does not rely on Golgi transport.…”

Section: Discussionmentioning

confidence: 89%

“…Also, pairing of C16:0 peptides with adjuvants that recruit moDCs to the site of injection such as AddaVax could be an interesting strategy. 46 …”

Section: Discussionmentioning

confidence: 99%

“…Immature moDCs were seeded in 96-well plates (Greiner Bio-One, Kremsmünster, Austria) at 20 × 10 3 cells/well and incubated with 10, 1, or 0.1 μM gp100 or C16:0 gp100 peptide. After 3 h, moDCs were washed and co-cultured o/n with gp100-specific CD8 + T cells 46 or the gp100-specific HLA-DRB1∗0401-restricted T cell line Bridge gp:44 B8, 45 at a concentration of 10 × 10 4 cells per well (effector to target cell [E:T] ratio of 1:5). IFNγ secretion in the supernatant was measured by sandwich ELISA.…”

Section: Methodsmentioning

confidence: 99%

“…To determine the effect of proteasomal and endosomal inhibitors, moDCs (20 × 10 3 cells/well) were incubated with chloroquine (50 μM, Sigma, Darmstadt, Germany), MG132 (50 μM, Selleckchem, Houston, TX, USA), bortezomib (10 nM, Sigma, Darmstadt, Germany), primaquine (50 μM, Sigma, Darmstadt, Germany), cathepsin S inhibitor (50 μM, Calbiochem, San Diego, CA, USA), leupeptin (15 μM, Calbiochem, San Diego, CA, USA), or vehicle (control is treated with the highest DMSO concentration used in the experiment; vehicle control peptide and C16:0 peptide are the same for all the inhibitors) for 30 min at 37°C prior and during the 3-h pulse with gp100, C16:0 gp100, or short peptide. After 3 h the DCs were washed and co-cultured with gp100-specific CD8 + T cells 46 (10 × 10 4 cells per well, E:T ratio of 1:5). IFNγ secretion, as a measure of T cell activation, was analyzed by sandwich ELISA (eBioscience, San Diego, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

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Palmitoylated antigens for the induction of anti-tumor CD8+ T cells and enhanced tumor recognition

Stolk

Horrevorts

Schetters

et al. 2021

Molecular Therapy - Oncolytics

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Induction of tumor-specific cytotoxic CD8 + T cells (CTLs) via immunization relies on the presentation of tumor-associated peptides in major histocompatibility complex (MHC) class I molecules by dendritic cells (DCs). To achieve presentation of exogenous peptides into MHC class I, cytosolic processing and cross-presentation are required. Vaccination strategies aiming to induce tumor-specific CD8 + T cells via this exogenous route therefore pose a challenge. In this study, we describe improved CD8 + T cell induction and in vivo tumor suppression of mono-palmitic acid-modified (C16:0) antigenic peptides, which can be attributed to their unique processing route, efficient receptor-independent integration within lipid bilayers, and continuous intracellular accumulation and presentation through MHC class I. We propose that this membrane-integrating feature of palmitoylated peptides can be exploited as a tool for quick and efficient antigen enrichment and MHC class I loading. Importantly, both DCs and non-professional antigen-presenting cells (APCs), similar to tumor cells, facilitate anti-tumor immunity by efficient CTL priming via DCs and effective recognition of tumors through enhanced presentation of antigens.

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Exploiting Unique Features of Microneedles to Modulate Immunity

et al. 2023

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Microneedle arrays (MNAs) are small patches containing hundreds of short projections that deliver signals directly to dermal layers without causing pain. These technologies are of special interest for immunotherapy and vaccine delivery because they directly target immune cells concentrated in the skin. The targeting abilities of MNAs result in efficient immune responses—often more protective or therapeutic—compared to conventional needle delivery. MNAs also offer logistical benefits, such as self‐administration and transportation without refrigeration. Thus, numerous preclinical and clinical studies are exploring these technologies. Here we discuss the unique advantages of MNA, as well as critical challenges – such as manufacturing and sterility issues – the field faces to enable widespread deployment. We explain how MNA design parameters can be exploited for controlled release of vaccines and immunotherapies, and the application to preclinical models of infection, cancer, autoimmunity, and allergies. We also discuss specific strategies to reduce off‐target effects compared to conventional vaccine delivery routes, and novel chemical and manufacturing controls that enable cargo stability in MNAs across flexible intervals and temperatures. We then examine clinical research using MNAs. We conclude with drawbacks of MNAs and the implications, and emerging opportunities to exploit MNAs for immune engineering and clinical use.This article is protected by copyright. All rights reserved

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Immunological dynamics after subcutaneous immunization with a squalene‐based oil‐in‐water adjuvant

Cited by 15 publications

References 52 publications

Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination

Adjuvant oncolytic virotherapy for personalized anti-cancer vaccination

Palmitoylated antigens for the induction of anti-tumor CD8+ T cells and enhanced tumor recognition

Exploiting Unique Features of Microneedles to Modulate Immunity

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