Academic Journal
Oncolytic virus encoding decorin and the CD40 ligand boosts T-cell response and achieves a durable antitumor response during breast cancer treatment.
| Τίτλος: | Oncolytic virus encoding decorin and the CD40 ligand boosts T-cell response and achieves a durable antitumor response during breast cancer treatment. |
|---|---|
| Συγγραφείς: | Ning Y; Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, 315010, China., Rong Y; Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, 315010, China., Meng H; The First Affiliated Hospital of Ningbo University, Ningbo, 315010, China., Lin Y; Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, 315010, China., Chen W; Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, 315010, China., Shi Q; Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, 315010, China., Zhang S; Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, 315010, China., Li H; Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, 315010, China. lihongshan_1982@126.com., Yang Y; Centre for Medical Research, Ningbo No.2 Hospital, Ningbo, 315010, China. yuefengyang1981@163.com.; Beijing Jingda Biotechnology Co. Ltd, Beijing, 102629, China. yuefengyang1981@163.com. |
| Πηγή: | Molecular biomedicine [Mol Biomed] 2026 Oct 05; Vol. 7 (1). Date of Electronic Publication: 2026 Oct 05. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer Singapore Country of Publication: Singapore NLM ID: 9918283581406676 Publication Model: Electronic Cited Medium: Internet ISSN: 2662-8651 (Electronic) Linking ISSN: 26628651 NLM ISO Abbreviation: Mol Biomed Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Singapore : Springer Singapore, [2020]- |
| Ιατρικοί όροι (MeSH): | Decorin*/genetics , Decorin*/metabolism , CD40 Ligand*/genetics , CD40 Ligand*/metabolism , Oncolytic Viruses*/genetics , Triple Negative Breast Neoplasms*/therapy , Triple Negative Breast Neoplasms*/immunology , Triple Negative Breast Neoplasms*/pathology , T-Lymphocytes*/immunology , Oncolytic Virotherapy*, Adenoviridae/genetics ; Dendritic Cells/immunology ; Animals ; Female ; Humans ; Cell Line, Tumor ; Mice ; Apoptosis ; Mice, Inbred BALB C |
| Περίληψη: | Triple-negative breast cancer (TNBC) remains an aggressive disease with limited treatment options. Oncolytic adenoviruses represent a promising platform, but their efficacy as single agents is often insufficient. This study examined whether an oncolytic adenovirus co-delivering decorin (DCN) and CD40 ligand (CD40L), designated rAd.DCN.CD40L, could enhance antitumor activity and immune activation against TNBC. Recombinant adenoviruses expressing DCN (rAd.DCN), CD40L (rAd.CD40L), or both proteins were constructed and evaluated in breast cancer cells using cell viability, apoptosis, migration, invasion, and damage-associated molecular pattern (DAMP) release assays. Compared with rAd.DCN or rAd.CD40L alone, rAd.DCN.CD40L triggered greater apoptosis and tumor cell death and elicited more pronounced DAMP release. Co-culture experiments also revealed enhanced dendritic cell function following rAd.DCN.CD40L treatment. For in vivo evaluation, syngeneic 4T1 and EMT-6 subcutaneous tumor models and a 4T1 lung metastasis model were employed. rAd.DCN.CD40L substantially delayed tumor growth and improved survival in tumor-bearing mice. Flow cytometric and histological analyses further confirmed enhanced local and systemic T-cell responses, elevated CD8⁺ T-cell activity, and modulated inflammatory macrophage phenotypes. Mechanistically, western blot analysis showed that rAd.DCN.CD40L may contribute to extracellular matrix remodeling and the down-regulation of the expression of epithelial-mesenchymal transition (EMT)-associated genes. Notably, CD8⁺ T-cell depletion markedly attenuated the therapeutic efficacy of rAd.DCN.CD40L, demonstrating that CD8⁺ T cells are critical functional effectors of tumor control. Collectively, these findings indicate that a DCN- and CD40L-armed oncolytic adenovirus represents a promising combinatorial strategy for TNBC immunotherapy, and warrants further preclinical and clinical investigation. (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: All animal experiments were conducted in accordance with institutional guidelines and were approved by the Institutional Animal Care and Use Committee (IACUC) of Guoke Ningbo Life Science and Health Industry Research Institute (Approval No.GK-2024-XM-1068). Consent for publication: Not applicable. Competing interests: Author Yuefeng Yang is an employee in Beijing Jingda Biotechnology Co. Ltd. The other authors have no conflicts of interest to declare. |
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| Grant Information: | LQ22H160008 Natural Science Foundation of Zhejiang Province; 2025HY1004 Medical Science and Technology Project of Zhejiang Province; 2024KY1550 Medical Science and Technology Project of Zhejiang Province; 2025HY1005 Medical Science and Technology Project of Zhejiang Province |
| Contributed Indexing: | Keywords: CD40L; Combination therapy; Decorin; Oncolytic adenoviruses; Triple-negative breast cancer; Tumor microenvironment |
| Substance Nomenclature: | 0 (Decorin) 147205-72-9 (CD40 Ligand) |
| Entry Date(s): | Date Created: 20261004 Date Completed: 20261005 Latest Revision: 20261007 |
| Update Code: | 20261007 |
| PubMed Central ID: | PMC13635066 |
| DOI: | 10.1186/s43556-026-00570-w |
| PMID: | 42830336 |
| Βάση Δεδομένων: | MEDLINE |
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