Talimogene Laherparepvec (T-VEC): Expanding Horizons in Oncolytic Viral Therapy Across Multiple Cancer Types

Talimogene laherparepvec (T-VEC), the first FDA-approved oncolytic viral therapy, has transformed cancer immunotherapy since its 2015 approval for unresectable melanoma. Engineered from Herpes Simplex Virus type 1 (HSV-1) with deletions in ICP34.5 and ICP47 genes and GM-CSF insertion, T-VEC selectively replicates within the tumor cells, inducing lysis and releasing tumor-derived antigens while stimulating systemic antitumor immunity through dendritic cell activation. Although extensively studied for melanoma, its potential extends beyond this malignancy, with emerging applications in breast cancer, Head and Neck Squamous Cell Carcinoma (HNSCC), and other solid tumors. This review synthesizes T-VEC's mechanism of action, leveraging dysregulated Ras signalling, impaired interferon pathways in cancer cells, its clinical outcomes, and safety profile across these indications. While prior literature emphasizes melanoma monotherapy and combinations with immune checkpoint inhibitors, less attention has been given to its efficacy in non-melanoma cancers and synergistic potential with chemotherapy or radiation therapy. By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges-systemic delivery, immune clearance, and biomarker development for patient selection-are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC's expanding role in cancer treatment, offering clinicians' and researchers' insights to optimize its therapeutic horizons across diverse malignancies.