In search of intrinsic factors that contribute to the distinctively strong immunogenicity of a non-mutated cancer/testis antigen, we found that NY-ESO-1 forms polymeric structures through disulfide bonds. NY-ESO-1 binding to immature dendritic cells was dependent on its polymeric structure and involved Toll-like receptor-4 (TLR4) on the surface of immature dendritic cells in mouse and human. Gene gun-delivered plasmid encoding the wild-type NY-ESO-1 readily induced T cell-dependent antibody (Ab) responses in wild-type C57BL/10 mice but not TLR4-knock-out C57BL/10ScNJ mice. Disrupting polymeric structures of NY-ESO-1 by cysteine-to-serine (Cys-to-Ser) substitutions lead to diminished immunogenicity and altered TLR4-dependence in the induced Ab response. To demonstrate its adjuvant effect, NY-ESO-1 was fused with a major mugwort pollen allergen Art v 1 and a tumor-associated antigen, carbonic anhydrase 9. Plasmid DNA vaccines encoding the fusion genes generated robust immune responses against otherwise non-immunogenic targets in mice. Polymeric structure and TLR4 may play important roles in rendering NY-ESO-1 immunogenic and thus serve as a potent molecular adjuvant. NY-ESO-1 thus represents the first example of a cancer/testis antigen that is a also damage-associated molecular pattern.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3199455 | PMC |
| http://dx.doi.org/10.1074/jbc.M111.280123 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
pH-Ultrasensitive Membranolytic Polyesters with Alternating Sequence of Ionizable and Hydrophobic Groups for Selective Oncolytic Therapy.
J Am Chem Soc
December 2024
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China.
Oncolytic therapy, inducing cell death via cell membrane lysis, holds considerable promise in cancer treatment. However, achieving precise control over the structure and function of oncolytic materials for highly selective oncolytic therapy is a key challenge in the context of the subtle differences between tumor and normal tissues/cells. Herein, we report the development of pH-ultrasensitive oncolytic polyesters (pOPs) with an alternating sequence of ionizable and hydrophobic groups.
View Article and Find Full Text PDFSpatially Selective Imaging in Color: What You See is What You Want.
Adv Sci (Weinh)
December 2024
Engineering Product Development, Singapore University of Technology and Design, Singapore, 487372, Singapore.
Spatially selective imaging (SSI) involves sampling a group of pixels from different positions on an encoded object to display a decoded image. Here, SSI is achieved by using off-axis cylindrical Fresnel lens arrays to decode multiple images from an encoded print of structural color pixels. Each image is optically retrieved by separately placing different "keys" (arrays of lenses in different pseudorandom configurations) over the same encoded print, and then each image is digitally reconstructed for visualization.
View Article and Find Full Text PDFIntegrating electrospun aligned fiber scaffolds with bovine serum albumin-basic fibroblast growth factor nanoparticles to promote tendon regeneration.
J Nanobiotechnology
December 2024
State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China.
Background: Electrospun nanofiber scaffolds have been widely used in tissue engineering because they can mimic extracellular matrix-like structures and offer advantages including high porosity, large specific surface area, and customizable structure. In this study, we prepared scaffolds composed of aligned and random electrospun polycaprolactone (PCL) nanofibers capable of delivering basic fibroblast growth factor (bFGF) in a sustained manner for repairing damaged tendons.
Results: Aligned and random PCL fiber scaffolds containing bFGF-loaded bovine serum albumin (BSA) nanoparticles (BSA-bFGF NPs, diameter 146 ± 32 nm) were fabricated, respectively.
Approaching coupled-cluster accuracy for molecular electronic structures with multi-task learning.
Nat Comput Sci
December 2024
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Machine learning plays an important role in quantum chemistry, providing fast-to-evaluate predictive models for various properties of molecules; however, most existing machine learning models for molecular electronic properties use density functional theory (DFT) databases as ground truth in training, and their prediction accuracy cannot surpass that of DFT. In this work we developed a unified machine learning method for electronic structures of organic molecules using the gold-standard CCSD(T) calculations as training data. Tested on hydrocarbon molecules, our model outperforms DFT with several widely used hybrid and double-hybrid functionals in terms of both computational cost and prediction accuracy of various quantum chemical properties.
View Article and Find Full Text PDFElectrochemical polymerized DL-phenylalanine modified carbon nanotube sensor for the selective and sensitive determination of caffeic acid with riboflavin.
Sci Rep
December 2024
Department of Civil, Environmental and Mechanical Engineering, University of Trento, Via Mesiano, 77, 38123, Trento, Italy.
In this study, DL-phenylalanine modified with a multiwall carbon nanotube paste electrode is used as advanced electrochemical sensor for analysing of 0.1 mM caffeic acid (CFA) with simultaneous detection of riboflavin (RFN). The developed sensors include electrochemically polymerized DL-phenylalanine (DL-PA) modified multiwall carbon nanotube paste electrode [DL-PAMMCNTPE] and bare multiwall carbon nanotube paste electrode [BMCNTPE].
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!