Emerging Oncolytic Viruses: Beyond Adenoviruses and Herpes Simplex Virus

Oncolytic virotherapy represents an innovative therapeutic modality in oncology, exploiting the selective tropism of viruses to target and eradicate malignant cells. Unlike conventional cancer treatments such as chemotherapy and radiotherapy, oncolytic viruses (OVs) exhibit a dual mechanism of action: direct tumor cell lysis and potent immune activation. This approach transforms tumors into in situ vaccines, generating durable anti-tumor immune memory. The field has garnered substantial attention following the regulatory approval of talimogene laherparepvec (T-VEC), a genetically engineered herpes simplex virus, for metastatic melanoma treatment-a watershed moment in oncolytic virotherapy. Recent advances in genetic engineering have significantly enhanced OV specificity and efficacy, addressing critical challenges including tumor-selective targeting and immune evasion. This review comprehensively examines the complex mechanisms underlying OV therapeutic action, clinical applications, and recent developments that position oncolytic virotherapy as a transformative strategy in contemporary cancer treatment.