Academic Journal
Systematic review and multilevel meta-analysis of preclinical survival outcomes of Zika virus-based oncolytic therapy in glioblastoma.
| Title: | Systematic review and multilevel meta-analysis of preclinical survival outcomes of Zika virus-based oncolytic therapy in glioblastoma. |
|---|---|
| Authors: | Caribé Sena A; Faculdade ZARNS, Salvador, Bahia, Brazil. arthurcaribe.17@hotmail.com., Santana MI; Faculdade ZARNS, Salvador, Bahia, Brazil., Pinto Costa Rocha V; Instituto de Tecnologias em Saúde, Universidade SENAI CIMATEC, Salvador, Bahia, Brazil., Miranda de Avellar L; Serviço de Neurocirurgia, Hospital Geral Roberto Santos, Salvador, Bahia, Brazil. |
| Source: | Journal of neurovirology [J Neurovirol] 2026 Aug 27; Vol. 32 (5). Date of Electronic Publication: 2026 Aug 27. |
| Publication Type: | Journal Article; Meta-Analysis; Systematic Review |
| Language: | English |
| Journal Info: | Publisher: Springer Country of Publication: United States NLM ID: 9508123 Publication Model: Electronic Cited Medium: Internet ISSN: 1538-2443 (Electronic) Linking ISSN: 13550284 NLM ISO Abbreviation: J Neurovirol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2011- : New York : Springer Original Publication: Houndmills, Basingstoke, Hampshire ; New York, NY : Stockton Press, c1995- |
| MeSH Terms: | Brain Neoplasms*/immunology , Brain Neoplasms*/mortality , Brain Neoplasms*/pathology , Brain Neoplasms*/therapy , Glioblastoma*/immunology , Glioblastoma*/mortality , Glioblastoma*/pathology , Glioblastoma*/therapy , Oncolytic Virotherapy*/methods , Oncolytic Viruses*/genetics , Oncolytic Viruses*/immunology , Oncolytic Viruses*/physiology , Zika Virus*/physiology , Zika Virus*/immunology , Zika Virus*/genetics, Immune Checkpoint Inhibitors/therapeutic use ; Neoplastic Stem Cells/virology ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/drug effects ; Animals ; Humans |
| Abstract: | Glioblastoma remains a highly lethal primary brain tumor with limited therapeutic options. Zika virus (ZIKV) has emerged as a candidate oncolytic platform because of its tropism for glioblastoma stem-like cells and its immunomodulatory potential. We conducted a systematic review and multilevel meta-analysis of preclinical in vivo studies evaluating ZIKV-based therapy in glioblastoma. Six studies met the eligibility criteria, yielding 27 survival-relevant experimental clusters, of which 24 entered the primary quantitative synthesis. The primary analysis included 38 survival contrasts nested within 24 clusters and showed a significant pooled survival benefit within the first 25 days of follow-up (ΔRMST = 2.66 days, 95% CI 1.80-3.52; CR2 p < 0.001). Heterogeneity was substantial, and the 95% prediction interval (- 1.60 to 6.92 days) crossed the null, indicating that benefit is expected on average but not uniformly across experimental contexts. Adding therapeutic platform improved model fit, but category estimates were based on few and unevenly distributed publications; the largest point estimate, for ZIKV combined with immune checkpoint blockade (ΔRMST = 3.93 days, 95% CI 2.72-5.14; two publications), is therefore descriptive and hypothesis-generating rather than comparative evidence. Sensitivity analyses using experiment-specific truncation horizons preserved the overall direction of effect but were not directly comparable in magnitude. ZIKV-based therapy shows context-dependent preclinical activity in glioblastoma; standardized efficacy, safety, and delivery studies are required before platform selection or clinical translation. (© 2026. The Author(s) under exclusive licence to The Journal of NeuroVirology, Inc.) |
| Competing Interests: | Declarations. Generative AI assistance in code development: Claude (Anthropic; Claude Sonnet 4.6) was used to assist with debugging the R and Python code, including identifying syntax errors, interpreting error messages, and suggesting code refactoring. The tool was not used to define the study design, select the statistical methods, modify the prespecified analytical strategy, interpret the results, or formulate the study conclusions. Ethics Approval and Consent: This study used previously published, non-identifiable data, including reconstructed pseudo-individual survival data from published Kaplan–Meier curves; therefore, formal ethics approval was not required. Conflict of interest: The authors declare no conflicts of interest related to the research, authorship, or publication of this paper. Competing interests: The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: Glioblastoma; Immune checkpoint blockade; Meta-analysis; Oncolytic virotherapy; Preclinical; RMST; Zika virus |
| Substance Nomenclature: | 0 (Immune Checkpoint Inhibitors) |
| Entry Date(s): | Date Created: 20260827 Date Completed: 20260827 Latest Revision: 20261010 |
| Update Code: | 20261010 |
| DOI: | 10.1007/s13365-026-01340-8 |
| PMID: | 42658351 |
| Database: | MEDLINE |
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