1118 The iodinated fluorescein derivative PV-10 enhances the antiviral activity of CD8+ T-Cells by inducing STING dimerization: implications for enhanced vaccine applications
Notice bibliographique
Résumé
<h3>Background</h3> Rose Bengal sodium (PV-10) has recently garnered attention for its anti-tumor cytotoxicity, safety profile, and efficacy in several cancer types. In a murine model of melanoma, PV-10 administration led to regression of untreated lesions and distant lung metastases. In the melanoma model, PV-10 treatment significantly enhanced CD8+ T-cell response, increased TNF-α production by CD8+ T cells, and improved overall survival. While these results demonstrate the potential of PV-10 as a vaccine adjuvant, significant knowledge gaps exist regarding the underlying mechanism of action behind this phenomenon. In this study, we investigate the involvement of the stimulator of interferon (IFN) genes (STING), a central innate immunity pathway, in PV-10-mediated immune activation. <h3>Methods</h3> PV-10 (10% solution of Rose Bengal sodium in 0.9% saline) was provided by Provectus Biopharmaceuticals, Inc. and stored at room temperature in light-proof containers. PV-10-mediated STING induction and dimerization were assessed using THP-1 human leukemia monocytic cells. CD8+ T-cells and dendritic cells (DCs) were cultured in the presence of cytokines, as described previously. Cytotoxicity analyses were performed by Alamar Blue assays. STING dimerization was determined by western blot and mass spectroscopy analysis. CD8+ T-cells were stimulated with synthetic peptides representing hepatitis B surface antigen (HBsAg) and T-cell response in primed CD8+ T-cell and HBsAg-expressing PLC/PRF/5 hepatoma cell co-culture was analyzed by ELISpot assay. <h3>Results</h3> THP-1 cells treated with 100 mM PV-10 showed STING dimerization with a 70 kDa band, in addition to the normal 35 kDa monomeric band. Additionally, pro-inflammatory cytokines and chemokines were significantly upregulated with longer PV-10 incubation times compared to untreated controls, including MCP-1, IP-10, VEGF-a, IL-18, IL-6, IL-8, and GM-CSF. A measurable increase in IFN-γ was also observed, altogether indicating that PV-10 treatment induces STING activation. Importantly, PV-10 treatment also significantly increased the number of IFN-γ ELISpots produced by HBsAg-primed CD8+ T-cells when exposed to the antigen-presenting PLC/PRF/5 cells. <h3>Conclusions</h3> This report demonstrates, for the first time, the ability of PV-10 to function as an effective agent to enhance targeted immune therapeutics, including antiviral vaccines. Our studies show its unique modulation of the STING pathway as a potential mechanism for this activity. We discuss, in detail, the experimental findings and the development of PV-10 for future clinical studies. <h3>Acknowledgements</h3> This work was funded in part by an award from the Kids Cancer Care Foundation of Alberta and the Alberta Children’s Hospital Foundation. <h3>Ethics Approval</h3> All study specimens were collected following informed consent and approval by the Health Research Ethics Board of Alberta (HREBA) (Ethics ID: HREBA.CC-16–0286).
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».