溶瘤免疫病毒疗法:在抗病毒的干草堆中寻找肿瘤抗原这根针。
Oncolytic immunovirotherapy: finding the tumor antigen needle in the antiviral haystack.
作者信息
Kendall Benjamin L, Vile Richard G
机构信息
Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Immunology, Mayo Clinic, Rochester, MN, USA.
出版信息
Immunotherapy. 2025 Jun;17(8):585-594. doi: 10.1080/1750743X.2025.2513853. Epub 2025 Jun 6.
Immunovirotherapy integrates the oncolytic capabilities of viruses with the modulation of the host immune system to establish robust tumor-specific immune responses. Oncolytic viruses (OVs) are natural or engineered viruses that specifically replicate in and lyse tumor cells, triggering inflammation which recruits immune effector cells to the site of infection. These conditions theoretically synergize with immune checkpoint blockade (ICB), which aids in establishing and maintaining tumor-infiltrating CD8 T cells. However, clinical data directly confirming synergy between OV and ICB therapy is limited despite ICB becoming the standard of care for several cancer types. It has been shown that viral immunodominance may limit antitumor T-cell priming and cause the attrition of tumor-specific T cells, limiting long-term therapeutic efficacy. To overcome these barriers, precise incorporation of virally expressed or exogenously administered tumor-associated antigens (TAAs) can synchronize the expansion of both antiviral and antitumor T cells, creating optimal conditions for ICB treatment. This tripartite approach leverages our understanding of antiviral immunity to efficiently expand subdominant antitumor T cells . In this review, we dissect the fundamental paradigm of immunovirotherapy regarding antiviral inflammation and TAAs, followed by relevant combinatorial strategies employed in preclinical and clinical settings for the treatment of solid tumors.
免疫病毒疗法将病毒的溶瘤能力与宿主免疫系统的调节相结合,以建立强大的肿瘤特异性免疫反应。溶瘤病毒(OVs)是天然或工程改造的病毒,它们在肿瘤细胞中特异性复制并裂解肿瘤细胞,引发炎症,将免疫效应细胞招募到感染部位。从理论上讲,这些情况与免疫检查点阻断(ICB)协同作用,有助于建立和维持肿瘤浸润性CD8 T细胞。然而,尽管ICB已成为几种癌症类型的标准治疗方法,但直接证实OV与ICB疗法之间协同作用的临床数据仍然有限。研究表明,病毒免疫优势可能会限制抗肿瘤T细胞的启动,并导致肿瘤特异性T细胞的损耗,从而限制长期治疗效果。为了克服这些障碍,精确整合病毒表达或外源性给予的肿瘤相关抗原(TAAs)可以同步抗病毒和抗肿瘤T细胞的扩增,为ICB治疗创造最佳条件。这种三方方法利用我们对抗病毒免疫的理解,有效地扩增次要的抗肿瘤T细胞。在这篇综述中,我们剖析了免疫病毒疗法在抗病毒炎症和TAAs方面的基本范式,随后介绍了在临床前和临床环境中用于治疗实体瘤的相关联合策略。