Omolekan Tolulope O, Folahan Joy T, Tesfay Mulu Z, Mohan Harikrishnan, Dutta Ojasvi, Rahimian Leila, Ferdous Khandoker Usran, Ghavimi Reza, Cios Aleksandra, Beng Timothy K, Francis Joseph, D'Auvergne Oswald, Borad Mitesh J, Kousoulas Konstantin G, DiGiuseppe Stephen, Nagalo Bolni Marius, Chamcheu Jean Christopher
Department of Pathological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States.
Front Immunol. 2025 Aug 25;16:1618751. doi: 10.3389/fimmu.2025.1618751. eCollection 2025.
Oncolytic virotherapy (OVT) has emerged as a promising and innovative cancer treatment strategy that harnesses engineered viruses to selectively infect, replicate within, and destroys malignant cells while sparing healthy tissues. Beyond direct oncolysis, oncolytic viruses (OVs) exploit tumor-specific metabolic, antiviral, and immunological vulnerabilities to reshape the tumor microenvironment (TME) and initiate systemic antitumor immunity. Despite promising results from preclinical and clinical studies, several barriers, including inefficient intratumoral virus delivery, immune clearance, and tumor heterogeneity, continue to limit the therapeutic advantages of OVT as a standalone modality and hindered its clinical success. Recent advances in OV engineering have enhanced viral tropism, immune evasion, and transgene delivery, enabling better tumor targeting and penetration and sustained immune activation in malignant tumors. Moreover, rational combination strategies with immune checkpoint inhibitors (ICIs), chemotherapeutics, and immunometabolic modulators are reshaping OVT into a versatile strategy for precision oncology. This review highlights the mechanistic innovations driving next-generation OV engineering, explores emerging combination regimens, and discusses future directions to overcome resistance and maximize clinical efficacy.
溶瘤病毒疗法(OVT)已成为一种有前景的创新性癌症治疗策略,该策略利用工程改造的病毒选择性地感染、在恶性细胞内复制并摧毁恶性细胞,同时保护健康组织。除了直接溶瘤作用外,溶瘤病毒(OVs)还利用肿瘤特异性的代谢、抗病毒和免疫弱点来重塑肿瘤微环境(TME)并启动全身性抗肿瘤免疫。尽管临床前和临床研究取得了有前景的结果,但包括瘤内病毒递送效率低下、免疫清除和肿瘤异质性在内的几个障碍,仍然限制了OVT作为单一治疗方式的治疗优势,并阻碍了其临床成功。OV工程的最新进展增强了病毒嗜性、免疫逃逸和转基因递送能力,从而实现更好的肿瘤靶向性和穿透性,并在恶性肿瘤中持续激活免疫。此外,与免疫检查点抑制剂(ICIs)、化疗药物和免疫代谢调节剂的合理联合策略正在将OVT重塑为一种用于精准肿瘤学的通用策略。本综述重点介绍了推动下一代OV工程的机制创新,探讨了新兴的联合治疗方案,并讨论了克服耐药性和最大化临床疗效的未来方向。