Oncolytic Virus Applications in Cancer Immunotherapy

Oncolytic viruses represent an emerging class of cancer therapeutics that combine direct lytic activity against malignant cells with potent immunostimulatory effects. By exploiting natural or engineered viral tropism, these agents preferentially replicate in tumour cells, causing immunogenic cell death and releasing tumour-associated antigens. This process recruits and activates dendritic cells, leading to T-cell priming and reshaping the immunosuppressive tumour microenvironment into an inflamed, immune-responsive niche. Genetic modifications enable precise control over viral replication, safety and payload delivery—such as cytokines or immune checkpoint modulators—enhancing both local oncolysis and systemic immunity. Clinically, oncolytic immunotherapy has demonstrated durable responses in melanoma, glioblastoma and other refractory cancers, particularly when combined with immune checkpoint blockade. Current research focuses on optimising delivery methods, evading antiviral neutralisation, fine-tuning cell-death pathways to amplify immunogenic signals and integrating personalised neoantigen–targeting strategies. Globally, oncolytic virotherapy holds promise for converting “cold” tumours into “hot” ones, broadening therapeutic options across diverse malignancies.

Research from Nature Portfolio

Recent clinical trials have validated the safety and immunological efficacy of engineered oncolytic herpesviruses in glioblastoma. A phase I study of CAN-3110, a nestin-promoter–driven herpes simplex virus type 1, demonstrated preferential tumour replication, absence of dose-limiting toxicities and enhanced T-cell clonal diversity correlating with extended survival in recurrent disease. A phase II trial of G47Δ, a triple-mutated oHSV, in residual or recurrent supratentorial glioblastoma reported an 84 % one-year survival rate and evidence of sustained CD4+ and CD8+ lymphocyte infiltration, leading to regulatory approval in Japan. Foundational preclinical work has further shown that pairing oncolytic vaccinia virus with PD-L1 blockade synergistically promotes effector T-cell infiltration and cytokine release in solid tumour models, providing a mechanistic basis for combinatorial strategies.

Oncolytic Virus Applications in Cancer Immunotherapy publication trend

The graph below shows the total number of articles in oncolytic virus applications in cancer immunotherapy across all publications each year (not limited to Nature Index journals).

Technical terms

Oncolytic virus: A virus engineered or naturally selected to preferentially infect and destroy cancer cells while stimulating antitumour immunity.

Tumour microenvironment: The cellular milieu surrounding a tumour, including immune cells, blood vessels and stromal elements that influence cancer progression and therapy response.

Immunogenic cell death: A form of cell death that releases danger signals and tumour antigens, promoting dendritic cell activation and adaptive immune responses.

Immune checkpoint blockade: Therapeutic inhibition of regulatory pathways, such as PD-1/PD-L1, to enhance T-cell–mediated antitumour activity.

References

1. Clinical trial links oncolytic immunoactivation to survival in glioblastoma. Nature (2023).
2. Intratumoral oncolytic herpes virus G47∆ for residual or recurrent glioblastoma: a phase 2 trial. Nature Medicine (2022).
3. Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy. Nature Communications (2017).
4. Reshaping the tumor microenvironment of cold soft-tissue sarcomas with oncolytic viral therapy: a phase 2 trial of intratumoral JX-594 combined with avelumab and low-dose cyclophosphamide. Molecular Cancer (2024).
5. Identification of restrictive molecules involved in oncolytic virotherapy using genome-wide CRISPR screening. Journal of Hematology & Oncology (2024).
6. Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial. Annals of Surgical Oncology (2016).