Core Viewpoint - Oncolytic viruses (OV) represent a promising therapy in cancer treatment, particularly for glioblastoma, by selectively replicating in tumor cells and activating immune responses [2][3][5]. Group 1: Clinical Trial Findings - A first-in-human phase 1 clinical trial reported safety data for 41 patients with recurrent glioblastoma (rGBM) treated with a modified oncolytic herpes simplex virus (oHSV), which selectively replicates in glioblastoma cells without harming healthy brain tissue [3]. - The treatment led to enhanced anti-cancer immune responses, with patient survival correlating with immune activation characteristics [3][4]. - Single oncolytic virus treatment resulted in deep and persistent T cell infiltration in glioblastoma, activating T cell-mediated cytotoxic responses associated with longer progression-free survival and overall survival [4][5]. Group 2: Immune Response Mechanisms - The study revealed that a single injection of oncolytic virus could transform the immune cold environment of glioblastoma into a hot environment rich in activated cytotoxic T cells, significantly extending patient survival [5]. - Evidence of early T cell activation and tissue residency was observed, with T cells near tumor cells expressing high levels of activation markers, indicating ongoing recognition of tumor antigens [8]. - The expansion of pre-existing tumor-infiltrating T cell clones was noted, correlating with longer overall survival, suggesting that the treatment amplifies existing immune responses [11]. Group 3: Treatment Challenges and Considerations - Despite strong T cell responses, hypoxic tumor regions exhibited T cell exclusion, potentially due to a suppressive microenvironment, which may contribute to treatment resistance [13]. - Long-term use of dexamethasone, a common medication for brain edema, was associated with reduced T cell clonality post-treatment, indicating a need for careful management of corticosteroids to optimize immune responses [14]. - The study emphasizes the importance of combining oncolytic virus therapy with agents that enhance T cell expansion and persistence, as well as anti-VEGF therapies to overcome hypoxic conditions [17].

Core Viewpoint - Oncolytic viruses (OV) represent a promising therapy for cancer treatment, selectively replicating in tumor cells to trigger anti-tumor responses, but systemic delivery remains a challenge due to pre-existing neutralizing antibodies and potential systemic toxicity [3][4]. Group 1 - The research team from Zhejiang University developed a systemically injectable oncolytic virus delivery platform called iNV-GOV, which protects viral particles from immune recognition and directs them to tumor sites, accelerating cancer cell pyroptosis and eliciting a strong anti-tumor immune response [4][5]. - The iNV-GOV platform integrates cancer virotherapy, cell membrane coating technology, CAR targeting, and controlled cell pyroptosis, addressing issues of low viral delivery efficiency and safety while significantly enhancing anti-tumor immune effects [5][7]. Group 2 - The engineered immune-compatible cell membrane expresses chimeric antigen receptors (CAR) to construct the tumor-targeting oncolytic virus delivery platform, functioning as an "invisibility cloak" to protect viral particles and as a "navigation" system to guide them to tumor sites [7]. - The viral load is controlled by a heat shock promoter, allowing ultrasound-induced mild hyperthermia to trigger tumor-specific cell pyroptosis, enhancing tumor lysis and promoting rapid release of oncolytic viruses from lysed tumor cells, thereby increasing infection of adjacent tumor cell populations [7][9]. Group 3 - Overall, this systemically injectable, tumor-targeting oncolytic virus platform enables rapid and sustained proliferation of viruses within tumors, providing a promising new strategy for treating various cancers [9].