1118 The iodinated fluorescein derivative PV-10 enhances the antiviral activity of CD8+ T-Cells by inducing STING dimerization: implications for enhanced vaccine applications
Bibliographic record
Abstract
<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).
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".