Abstract
917 Treatment with virus-like particles containing a TLR9-agonist enhances and extends the activation of tumor-specific CD8+ T cells
Journal for immunotherapy of cancer, Vol.13(Suppl 2), pp.A1040-A1040
11/01/2025
DOI: 10.1136/jitc-2025-SITC2025.0917
Abstract
Background Cytotoxic CD8+ T cells are pivotal in antitumor immunity, but their effectiveness can be hindered by exhaustion within the tumor microenvironment (TME). Vidutolimod, a virus-like particle composed of a CpG-A toll-like receptor (TLR) 9 agonist encapsulated by Qβ capsid protein, enhances immune activation and has shown therapeutic potential in preclinical models and clinical trials. This study investigates the impact of Vidutolimod on tumor-specific CD8+ T cell activation, functionality, and exhaustion.MethodsOT-1 mice, which contain transgenic CD8+ T cells specific for the ovalbumin epitope SIINFEKL, were cultured and stimulated with OVA+ tumor cells or SIINFEKL peptide, with or without Vidutolimod treatment. T cell activation, proliferation, and inhibitory marker expression were assessed via flow cytometry. In vivo, Vidutolimod-treated mice bearing EG7-OVA tumors received OT-1 T cell transfers followed by intratumoral Vidutolimod injections. Tumor-specific T cell infiltration, phenotype, and survival outcomes were analyzed.ResultsIn vitro, Vidutolimod treatment decreased CD8+ T cell proliferation but enhanced their effector molecule expression (e.g., CD25, IFNγ, Granzyme B). Vidutolimod-treated CD8+ T cells also displayed greater cytotoxicity, especially at lower Effector:Target ratios. Despite increased inhibitory marker expression initially, CD8+ T cells retained functionality, with reduced signs of terminal exhaustion over time. In vivo, Vidutolimod-treated mice showed significantly increased survival, reduced tumor burden, and elevated tumor-specific CD8+ T cells in the tumor and circulation. Vidutolimod-treated mice had tumor-specific CD8+ T cells that exhibited decreased PD-1 expression in the TME compared to saline-treated mice. Conversely, circulating tumor-specific CD8+ T cells in Vidutolimod-treated mice expressed higher levels of PD-1 than saline-treated counterparts.ConclusionsIn vitro, Vidutolimod treatment enhanced the cytotoxicity and effector molecule production by tumor-specific CD8+ T cells. In vivo, Vidutolimod increased the influx of tumor-specific CD8+ T cells into the primary tumor and elevated their numbers in circulation. Vidutolimod also increased the frequency of circulating PD-1+ OT-1 T cells, supporting further evaluation of anti-PD-1 therapy in combination with Vidutolimod. Taken together, our findings highlight the immunostimulatory effects of Vidutolimod on tumor-specific CD8+ T cells and provides insight into prior studies that demonstrated an enhanced anti-tumor response with Vidutolimod treatment, especially in combination with anti-PD-1 therapy.Ethics ApprovalMouse studies were approved by and performed according to guidelines established by the University of Iowa Institutional Animal Care and Use Committee under an approved IACUC Protocol #3011236.
Details
- Title: Subtitle
- 917 Treatment with virus-like particles containing a TLR9-agonist enhances and extends the activation of tumor-specific CD8+ T cells
- Creators
- Travis Fischer - University of IowaCaitlin Lemke-Miltner - University of IowaGeorge Weiner - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Journal for immunotherapy of cancer, Vol.13(Suppl 2), pp.A1040-A1040
- DOI
- 10.1136/jitc-2025-SITC2025.0917
- eISSN
- 2051-1426
- Publisher
- BMJ Publishing Group LTD
- Language
- English
- Date published
- 11/01/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9985024258702771
Metrics
1 Record Views