Journal article
In situ treatment with a TLR9 agonist virus-like particle to promote immune responses against oral epithelial dysplasia progression
Cancer immunology, immunotherapy, Vol.74(6), 189
05/03/2025
DOI: 10.1007/s00262-025-04023-1
PMCID: PMC12049351
PMID: 40317310
Abstract
Leukoplakia, a common type of oral dysplasia, is simply defined as a white patch in the mouth or other mucosal surface. Oral dysplasia is the most common premalignancy in the oral cavity and yet it is insufficiently researched and thus both diagnosing and treating oral dysplasia are still problematic issues. This study focuses on the immune signature of oral dysplasia and explores whether stimulating the immune system with an immune therapy, vidutolimod (± immune checkpoint blockade (ICB)), can prevent the progression of oral dysplasia or even cause regression. Vidutolimod, a virus-like particle encapsulating G10, is believed to activate plasmacytoid dendritic cells (pDCs) through the activation of the Toll-like receptor 9 (TLR9). To investigate this, an established murine model for inducing oral cancer was used to study oral dysplasia development and response to in situ injection of vidutolimod at the premalignant phase. The effect of treatment was analyzed histologically and immunologically. ELISA revealed significantly elevated levels of IFN-γ, IL-12, and TNF-α in the sera of mice after 24 h of one treatment with vidutolimod + ICB as well as increased levels of proliferating T cells and pDCs in draining lymph nodes 72 h after the third and final treatment, thus indicating the immune-boosting effect of this therapy. Vidutolimod + ICB caused a significant decrease in Ki-67 expression by epithelial cells in the lesion area compared to untreated mice, implicating that this treatment regime may prevent lesion progression.
Details
- Title: Subtitle
- In situ treatment with a TLR9 agonist virus-like particle to promote immune responses against oral epithelial dysplasia progression
- Creators
- Yan Xu - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of IowaAlexandra Mcmillan - University of IowaNikesh Gupta - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of IowaCaitlin D. Lemke-Miltner - University of IowaAseel O. Rataan - University of IowaSudartip Areecheewakul - University of IowaDivya S. Bhat - University of IowaEmily A. Lanzel - University of IowaSean M. Geary - University of IowaAndrean L. Simons - University of Iowa, Radiation OncologyGeorge J. Weiner - University of IowaAliasger K. Salem - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Holden Comprehensive Cancer Center, The University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer immunology, immunotherapy, Vol.74(6), 189
- DOI
- 10.1007/s00262-025-04023-1
- PMID
- 40317310
- PMCID
- PMC12049351
- NLM abbreviation
- Cancer Immunol Immunother
- ISSN
- 0340-7004
- eISSN
- 1432-0851
- Publisher
- Springer Berlin Heidelberg
- Language
- English
- Date published
- 05/03/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Oral Pathology, Radiology and Medicine; Research Administration; Hematology, Oncology, and Blood & Marrow Transplantation; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984816011702771
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