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Oncolytic virotherapy for cancer: biological mechanisms, clinical advances, and future perspectives.

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Τίτλος: Oncolytic virotherapy for cancer: biological mechanisms, clinical advances, and future perspectives.
Συγγραφείς: Halawa EM; Department of Botany and Microbiology, Faculty of Science, Cairo University, Giza, 12613, Egypt. esraahalawa@gstd.sci.cu.edu.eg., AbdelHamid SG; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt., ElHefnawi M; Biomedical Informatics and Chemoinformatics Group, Informatics and Systems Department, National Research Centre, Tahrir Street, Cairo, 12311, Egypt. Mahef111@gmail.com.
Πηγή: Clinical and experimental medicine [Clin Exp Med] 2026 Oct 16; Vol. 26 (1). Date of Electronic Publication: 2026 Oct 16.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer-Verlag Italia Country of Publication: Italy NLM ID: 100973405 Publication Model: Electronic Cited Medium: Internet ISSN: 1591-9528 (Electronic) Linking ISSN: 15918890 NLM ISO Abbreviation: Clin Exp Med Subsets: MEDLINE
Imprint Name(s): Original Publication: Milano, Italy: Springer-Verlag Italia, c2001-
Ιατρικοί όροι (MeSH): Oncolytic Virotherapy*/methods , Oncolytic Virotherapy*/trends , Neoplasms*/therapy , Neoplasms*/immunology , Oncolytic Viruses*/genetics , Oncolytic Viruses*/physiology, Immunotherapy/methods ; Humans ; Animals ; Tumor Microenvironment
Περίληψη: Oncolytic virotherapy has emerged as a promising cancer treatment that combines selective tumor destruction with potent stimulation of antitumor immunity. Unlike conventional therapies, oncolytic viruses (OVs) preferentially infect and replicate within malignant cells while sparing normal tissues, leading to direct tumor lysis and the release of tumor-associated antigens, pathogen-associated molecular patterns, and damage-associated molecular patterns that activate both innate and adaptive immune responses. Advances in molecular virology and genetic engineering have transformed naturally occurring viruses into programmable therapeutic platforms capable of delivering immunomodulatory payloads that enhance antitumor efficacy and remodel the tumor microenvironment. Multiple DNA- and RNA-based viral platforms, including herpes simplex virus, adenovirus, vaccinia virus, reovirus, measles virus, Newcastle disease virus, vesicular stomatitis virus, and coxsackievirus, are currently under clinical investigation, with regulatory approval of talimogene laherparepvec (T-VEC) and G47Δ providing important proof of clinical feasibility. Increasing evidence indicates that OVs can convert immunologically "cold" tumors into "hot" tumors, thereby improving responsiveness to immune checkpoint inhibitors and other therapeutic modalities. Consequently, oncolytic virotherapy has become an attractive component of combination strategies involving immunotherapy, chemotherapy, radiotherapy, targeted therapies, and cellular therapies. Nevertheless, several challenges continue to limit its broader clinical application, including antiviral immune clearance, inefficient systemic delivery, restricted intratumoral spread, tumor heterogeneity, manufacturing complexity, and the lack of robust predictive biomarkers. This review provides a comprehensive overview of the biological foundations of oncolytic virotherapy, viral engineering strategies, mechanisms of tumor selectivity, direct oncolysis, immunogenic cell death, and immune remodeling of the tumor microenvironment. It further summarizes the major oncolytic virus platforms, recent preclinical and clinical advances, emerging combination strategies, current translational challenges, and future directions expected to advance precision oncolytic virotherapy and expand its role in modern cancer treatment.
(© 2026. The Author(s).)
Competing Interests: Declarations. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Ethics approval and consent to participate: Not Applicable.
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Contributed Indexing: Keywords: Cancer immunotherapy; Combination therapy; Immunogenic cell death; Oncolytic virotherapy; Oncolytic viruses; Precision oncology; Tumor microenvironment; Viral engineering
Entry Date(s): Date Created: 20261016 Date Completed: 20261016 Latest Revision: 20261019
Update Code: 20261019
PubMed Central ID: PMC13675364
DOI: 10.1007/s10238-026-02311-3
PMID: 42886257
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1591-9528
DOI:10.1007/s10238-026-02311-3