Next-generation Oncolytic Virotherapy: Genetic Engineering, Immune Modulation, Advanced Delivery Platforms and Clinical Progress
Indu Arora, Shalu Attar, Priyanka Bhardwaj, Nancy, Tawqeer Shafi, Shafkat Hussain, Md Moidul Islam, Mohammad AkramIntroduction:
Oncolytic Virotherapy (OVT) is an emerging area of cancer immunotherapy that has shown promise as a therapeutic agent, leveraging genetically engineered replication- competent viruses that kill cancer cells without harming normal cells. HSV-1 (T-VEC), vaccinia, and adenoviruses. Immuno-Oncology Oncol Ther 2017; Monkey 7: 118 (HSV-1 (T-VEC), vaccinia, and adenoviruses also target tumor-specific dysregulations in pathways such as p53, Rb, IFN/PKR, and RAS-MAPK to induce cytolysis and immune activation).
Methods:
The keywords used for the literature review were strategic and included oncolytic virotherapy, tumor-specific lysis, immunogenic cell death, viral gene deletions, immune checkpoint synergy, and advanced delivery platforms. Articles in Scopus, PubMed, ScienceDirect, and Google Scholar were retrieved that were relevant for this purpose. Only recent, peer-reviewed publications published in English were included to ensure the quality, consistency, and reliability of the review.
Results:
These immunostimulatory cues convert the immunologically cold tumors into hot, T-cell-inflamed lesions. Improved immune infiltration is achieved through vascular-targeting (e.g., VSV, HSV-1716) and matrix-modifying effects. Newcastle disease virus, coxsackievirus, measles, poliovirus, and Maraba virus all expand the therapeutic arsenal, namely addressing preexisting immunity and intratumoral spread. New delivery platforms, such as mesenchymal stem cells, CAR-T cells, and biomineral-coated vesicles, are expected to enhance systemic circulation and targeting of metastatic sites.
Discussion:
There is synergistic antitumor activity when immune checkpoint blockade and adoptive T-cell therapy are combined with chemotherapy. However, there are still obstacles, such as antiviral clearance, stromal barriers, and the lack of biomarkers for predictive response.
Conclusion:
OVT is rapidly transitioning into a mainstream immuno-oncology platform through iterative engineering, effective innovative carriers, and rational multimodal regimens that provide sustained and systemic cancer control.