Journal article
Intratumoral virus-like particles containing a TLR9-agonist combined with systemic αPD-1 activate tumor-specific CD8+ T cells
Cancer research communications, Vol.6(5), pp.1006-1019
05/2026
DOI: 10.1158/2767-9764.CRC-26-0175
PMID: 41960903
Abstract
One strategy for enhancing the anti-cancer immune response is to inject tumors with immunostimulatory agents that modify the tumor microenvironment (TME) to induce a stronger anti-tumor T cell response. In situ immunization with Vidutolimod, a virus-like particle containing a CpG-A TLR9 agonist, has demonstrated anti-tumor activity in pre-clinical and early phase clinical studies, however its effect on tumor-specific CD8⁺ T cells remain poorly defined. Using the OT-1 model, we assessed how Vidu impacts activation, cytotoxicity, and anti-tumor activity of tumor-specific CD8⁺ T cells in vitro and in vivo. In vitro, Vidu reduced proliferation but increased expression of both activation and exhaustion markers. In vivo, repeated intratumoral Vidu injections induced a transient increase in the frequency of intratumoral tumor-specific CD8+ T cells and enhanced anti-tumor activity. The addition of αPD-1 to Vidu led to a persistent increase in intratumoral tumor-specific CD8+ T cells and sustained tumor control. Vidu treatment increased expression of markers associated with terminal exhaustion on intratumoral tumor-specific CD8⁺ T cells. Such treatment also increased the number of circulating tumor-specific CD8⁺ T cells that expressed high PD-1 but lacked co-expression of other exhaustion markers. Together, these findings demonstrate Vidu treatment expands the number of intratumoral and circulating tumor-specific CD8⁺ T cells, and that the number of tumor specific CD8+ T cells and the anti-tumor response is sustained by the addition of αPD-1. These results support continued evaluation of Vidu as a cancer immunotherapeutic agent, including in combination with immune checkpoint blockade.
Details
- Title: Subtitle
- Intratumoral virus-like particles containing a TLR9-agonist combined with systemic αPD-1 activate tumor-specific CD8+ T cells
- Creators
- Travis D Fischer - University of IowaCaitlin D Lemke-Miltner - University of IowaGeorge J Weiner - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Cancer research communications, Vol.6(5), pp.1006-1019
- DOI
- 10.1158/2767-9764.CRC-26-0175
- PMID
- 41960903
- NLM abbreviation
- Cancer Res Commun
- ISSN
- 2767-9764
- eISSN
- 2767-9764
- Publisher
- AACR
- Grant note
- National Institutes of Health (NIH): P30CA086862 Regeneron Pharmaceuticals (Regeneron)
This study was supported in part by the National Cancer Institute of the National Institutes of Health under Award Number P30CA086862 and received support from Regeneron Pharmaceuticals. Some of data presented herein were obtained at the University of Iowa Flow Cytometry Core Facility, a Carver College of Medicine and Holden Comprehensive Cancer Center core research facility. The facility is funded through user fees and the generous financial support of the Carver College of Medicine, Holden Comprehensive Cancer Center, and Iowa City Veteran's Administration Medical Center. Research reported in this publication was supported by the National Institutes of Health under Award Number 1 S10 OD034193-01. We thank the NIH Tetramer Core Facility (NIH Contract 75N93020D00005 and RRID: SCR_026557) for providing the H2-Kb, chicken ova 257-264 SIINFEKL, PE tetramer stain.
- Language
- English
- Electronic publication date
- 04/09/2026
- Date published
- 05/2026
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9985153399302771
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