Gene Therapy for Malignant Tumors: Focused on Immunostimulatory Oncolytic Coxsackievirus A11 (CVA11)

Gene therapy has emerged as a promising therapeutic strategy in oncology by targeting the molecular mechanisms that drive malignant transformation. Among gene-based approaches, oncolytic viruses (OVs) are distinctive in their ability to selectively replicate within tumor cells, induce direct oncolysis, and simultaneously stimulate systemic antitumor immunity by exploiting defects in cancer cell antiviral responses. Recent studies have identified Coxsackievirus A11 (CVA11) as a highly potent immunostimulatory OV. CVA11 demonstrates strong tumor-selective replication, robust cytolytic activity, and marked induction of antitumor immune responses. Notably, CVA11 has been shown to induce complete tumor regression in human non–small cell lung cancer models. In addition, CVA11 enhances chemosensitivity in oxaliplatin-resistant colorectal cancer and may have broader applicability in treatment-refractory malignancies, including pancreatic cancer. This review summarizes current gene therapy strategies for malignant tumors with a particular focus on the biological properties and therapeutic potential of CVA11. We discuss its mechanisms of tumor selectivity, immune activation, and potential integration with chemotherapy and gene-based cancer vaccines. Collectively, these findings position CVA11 as a promising next-generation oncolytic virus for cancer gene therapy and immunotherapy.