Academic Journal
Treatment sequence of stem cell delivered heterologous oncolytic virus impact on tumor microenvironment in immunocompetent ovarian cancer model.
| Τίτλος: | Treatment sequence of stem cell delivered heterologous oncolytic virus impact on tumor microenvironment in immunocompetent ovarian cancer model. |
|---|---|
| Συγγραφείς: | Abd El-Fattah EE; Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute of City of Hope, Duarte, CA, United States., Flores L; Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute of City of Hope, Duarte, CA, United States., Lara J; Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute of City of Hope, Duarte, CA, United States., Ngai G; Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute of City of Hope, Duarte, CA, United States., Mooney R; Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute of City of Hope, Duarte, CA, United States., Aboody K; Department of Stem Cell Biology and Regenerative Medicine, Beckman Research Institute of City of Hope, Duarte, CA, United States. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Aug 31; Vol. 17, pp. 1898617. Date of Electronic Publication: 2026 Aug 31 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Ovarian Neoplasms*/therapy , Ovarian Neoplasms*/immunology , Ovarian Neoplasms*/pathology , Oncolytic Virotherapy*/methods , Tumor Microenvironment*/immunology , Oncolytic Viruses*/genetics , Oncolytic Viruses*/immunology , Mesenchymal Stem Cells*, Vaccinia virus/genetics ; Adenoviridae/genetics ; Dendritic Cells/immunology ; Female ; Animals ; Mice ; Humans ; Mice, Inbred C57BL ; Disease Models, Animal ; Cell Line, Tumor ; Immunocompetence |
| Περίληψη: | Introduction: Ovarian cancer (OC) is a biologically heterogeneous malignancy associated with poor clinical outcomes. Oncolytic viruses (OVs) have emerged as a promising immunotherapeutic strategy; however, optimal approaches to maximize their antitumor efficacy-especially in combinatorial or sequential settings-remain insufficiently defined. To determine how the sequence of administration of two clinically relevant, stem cell-delivered OV platforms influences tumor control and immune remodeling in an immunocompetent OC model. Methods: We investigated the sequence of two clinically relevant products: neural stem cell delivered conditionally replication competent adenovirus (NSC.CRAd-S-pk7; NNV24) and a mesenchymal stem cell delivered vaccinia virus (MSC.VP001; SNV1). Female C57BL/6 mice were randomized into three groups: untreated tumor-bearing controls, NNV24 followed by SNV1 (NNV24+SNV1), or SNV1 followed by NNV24 (SNV1+NNV24). Therapeutic efficacy and immune responses were assessed by overall survival, histopathological evaluation, flow cytometric analysis of dendritic cell (DC) subsets and cytotoxic T lymphocytes (CTLs), and bulk RNA sequencing. Results: Treatment regimens initiated with NNV24 significantly prolonged survival compared with SNV1-first sequences. NNV24+SNV1 treatment resulted in enhanced intratumoral viral localization, increased infiltration of CTLs, mature DCs, and concomitant with a reduction in tolerogenic DC populations. Transcriptomic profiling corroborated these findings through revealing suppression of immunoregulatory and tolerogenic pathways signaling in comparison to SNV1+NNV24 group. Discussion: The treatment sequence of heterologous OV has a significant effect on the tumor microenvironment. NNV24+SNV1 promotes robust antitumor immunity and improved survival, whereas the reverse sequence compromises immune activation and therapeutic response. These findings establish a mechanistic framework for rational sequencing of OV-based immunotherapies. (Copyright © 2026 Abd El-Fattah, Flores, Lara, Ngai, Mooney and Aboody.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Contributed Indexing: | Keywords: adenovirus; immune modulation; oncolytic virotherapy; ovarian cancer; vaccinia virus |
| Entry Date(s): | Date Created: 20260915 Date Completed: 20260915 Latest Revision: 20260916 |
| Update Code: | 20260916 |
| PubMed Central ID: | PMC13572156 |
| DOI: | 10.3389/fimmu.2026.1898617 |
| PMID: | 42741068 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
|---|---|
| DOI: | 10.3389/fimmu.2026.1898617 |