Development of Oncolytic Viruses as Platforms for Drug Delivery to Cancers

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Gene and Cell Therapy".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 852

Special Issue Editors


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Guest Editor
Fondazione Banca dei Tessuti del Veneto ETS, 31100 Treviso, Italy
Interests: oncolytic viruses; herpes simplex virus type 1; gene therapy; tumor immunology

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Guest Editor
Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany
Interests: oncolytic viruses; immunotherapy; hepatocellular carcinoma; pancreatic cancer
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Special Issue Information

Dear Colleagues,

Oncolytic viruses (OVs) are a promising and emerging class of antitumoral therapeutics that selectively target cancer cells by exploiting defects in intrinsic antiviral pathways or the presence of specific receptors. While only one OV has been clinically approved so far by the FDA and the EMA, numerous trials are ongoing, and it is therefore conceivable that over the next years there will be more OVs available in clinical practice as new weapons against difficult-to-treat tumors. One of the most interesting features of these vectors is their versatility, which allows OVs to combine direct cytotoxicity, an immunotherapeutic mechanism of action, and the delivery of therapeutic genes and/or drugs to cancers. Most OVs can be engineered to directly encode therapeutic genes, encompassing biological drugs such as immune checkpoint inhibitors. Therefore, a very active area of research in oncolytic virotherapy is the identification and optimization of the best drugs and therapeutic genes to maximize the treatment efficacy. This Special Issue of Pharmaceutics will be focused on the development of oncolytic viruses as platforms for the targeted delivery of drugs to tumors, including both therapeutic genes encoded by the viral genome and proteins or small molecules that can be attached to viral particles before administration.

Dr. Alberto Reale
Dr. Jennifer Altomonte
Guest Editors

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Keywords

  • oncolytic viruses
  • cancer
  • targeted drug delivery
  • immunotherapy
  • gene therapy
  • tumor microenvironment

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Published Papers (1 paper)

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Review

20 pages, 835 KB  
Review
Fire in an Icy Desert: Oncolytic Virotherapy for Pancreatic Adenocarcinoma
by Alessandra Rossetto and Alberto Reale
Pharmaceutics 2026, 18(4), 510; https://doi.org/10.3390/pharmaceutics18040510 - 20 Apr 2026
Viewed by 429
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, characterized by early metastasis, dense desmoplastic stroma and a profoundly immunosuppressive, lymphocyte-depleted tumor microenvironment that severely limits the efficacy of current systemic and immunotherapeutic approaches. Oncolytic viruses (OVs), which selectively replicate in and [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, characterized by early metastasis, dense desmoplastic stroma and a profoundly immunosuppressive, lymphocyte-depleted tumor microenvironment that severely limits the efficacy of current systemic and immunotherapeutic approaches. Oncolytic viruses (OVs), which selectively replicate in and lyse malignant cells while activating antitumor immunity, have emerged as attractive candidates to convert this “cold” tumor into a more inflamed and therapeutically responsive disease. In this review, we summarize clinical evidence on the main OV platforms evaluated in PDAC, including adenovirus, herpes simplex virus, vaccinia virus, parvovirus and reovirus, with a focus on clinical trials. Across these classes of viruses, intratumoral administration has consistently proven feasible and generally well tolerated, with frequent evidence of viral replication, microenvironmental remodeling and immune activation, but only modest and often transient antitumor responses in small, early-phase cohorts. We then discuss key biological and translational challenges that currently limit OV impact in PDAC, such as systemic delivery in the context of pre-existing antiviral immunity and rapid clearance, penetration through the fibrotic stroma, and rational selection of encoded transgenes to reshape myeloid cell-driven, pro-tumoral inflammation and enhance T-cell recruitment. Finally, we outline future directions for the field, including carrier-cell–based systemic delivery, stroma-targeting or cytokine-armed constructs, and combinatorial strategies with chemotherapy and immune checkpoint blockade, arguing that design refinement, innovative combinations and mechanism-driven trial designs will be essential to unlock the full therapeutic potential of oncolytic virotherapy in PDAC. Full article
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