Division of Veterinary Microbiology and Immunology, Faculty of Veterinary Science and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology of Jammu, R.S. Pura, Jammu, Jammu & Kashmir, India; Department of Biomedicine, Aarhus University, Denmark.
Division of Veterinary Microbiology and Immunology, Faculty of Veterinary Science and Animal Husbandry, Sher-e-Kashmir University of Agricultural Sciences and Technology of Jammu, R.S. Pura, Jammu, Jammu & Kashmir, India.
Virology. 2024 Dec;600:110238. doi: 10.1016/j.virol.2024.110238. Epub 2024 Sep 11.
Oncolytic viruses, defined as viruses capable of lysing cancer cells, emerged as a groundbreaking class of therapeutic entities poised to revolutionize cancer treatment. Their mode of action encompasses both direct tumor cell lysis and the indirect enhancement of anti-tumor immune responses. Notably, four leading contenders in this domain, Rigvir® in Latvia, T-VEC in the United States, H101 in China and Teserpaturev (DELYTACT®) in Japan, have earned approval for treating metastatic melanoma (Rigvir and T-VEC), nasopharyngeal carcinoma and malignant glioma, respectively. Despite these notable advancements, the integration of oncolytic viruses into cancer therapy encounters several challenges. Foremost among these hurdles is the considerable variability observed in clinical responses to oncolytic virus interventions. Moreover, the adaptive immune system may inadvertently target the oncolytic viruses themselves, diverting immune resources away from tumor antigens and undermining therapeutic efficacy. Another significant limitation arises from the presence of preexisting immunity against oncolytic viruses in certain patient populations, hampering treatment outcomes. To circumvent this obstacle, researchers are investigating the utilization of animal viruses, for which humans lack preexisting immunity, as a compelling alternative to human-derived counterparts. In our comprehensive review, we delve into the intricate nuances of oncolytic virotherapy, elucidating the multifaceted mechanisms through which these viruses exert their anti-cancer effects. Furthermore, we provide a thorough examination of animal-derived oncolytic viruses, highlighting their respective strengths and limitations. Lastly, we explore the promising potential of leveraging animal viruses as potent oncolytic agents, offering new avenues for enhancing the efficacy and reach of human cancer therapeutics.
溶瘤病毒是指能够裂解癌细胞的病毒，它们作为一类开创性的治疗实体出现，有望彻底改变癌症治疗方式。它们的作用模式包括直接裂解肿瘤细胞和间接增强抗肿瘤免疫反应。值得注意的是，在该领域的四个领先候选药物，拉脱维亚的 Rigvir®、美国的 T-VEC、中国的 H101 和日本的 Teserpaturev（DELYTACT®），分别获得批准用于治疗转移性黑色素瘤（Rigvir 和 T-VEC）、鼻咽癌和恶性胶质瘤。尽管取得了这些显著进展，但溶瘤病毒在癌症治疗中的应用仍面临一些挑战。其中最主要的障碍是观察到对溶瘤病毒干预的临床反应存在相当大的可变性。此外，适应性免疫系统可能会无意中针对溶瘤病毒本身，转移免疫资源远离肿瘤抗原，从而削弱治疗效果。另一个重要的限制因素是某些患者群体中存在针对溶瘤病毒的预先存在的免疫，从而影响治疗效果。为了克服这一障碍，研究人员正在研究利用动物病毒作为人类来源的病毒的替代品，因为人类对动物病毒缺乏预先存在的免疫。在我们的全面综述中，我们深入探讨了溶瘤病毒治疗的复杂细节，阐明了这些病毒发挥抗癌作用的多方面机制。此外，我们对动物来源的溶瘤病毒进行了全面检查，突出了它们各自的优缺点。最后，我们探讨了利用动物病毒作为有效的溶瘤剂的有前景的潜力，为增强人类癌症治疗的疗效和范围提供了新的途径。
