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Phase I trial of intravenous VCN-01 oncolytic adenovirus and durvalumab in patients with head and neck metastatic squamous cell carcinoma refractory to immunotherapy

ABSTRACT: VCN-01 is a hyaluronidase-expressing oncolytic adenovirus that increases immune checkpoint antibody tumor uptake in mice. VCN-01 was evaluated with durvalumab in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients refractory to anti-PD-(L)1

ORGANISM(S): Homo sapiens

PROVIDER: GSE333537 | GEO | 2026/06/03

REPOSITORIES: GEO

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Project description:Abstract Background: YSCH-01, a recombinant L-IFN adenovirus injection, is an oncolytic virus- based anticancer drug with dual anti-tumor effects. In previous studies, we have confirmed the potential of YSCH-01 in the treatment of malignant gliomas. Additionally, YSCH-01 has emerged as a promising candidate for osteosarcoma treatment, exhibiting significant antitumor properties. However, its specific role in osteosarcoma and the underlying mechanisms remain poorly understood. Methods: We evaluated the infectivity and efficacy of YSCH-01 in osteosarcoma cells by collecting clinical samples of osteosarcoma and conducting experiments using osteosarcoma cell lines both in vitro and in vivo. Additionally, we studies the impact of YSCH-01 on interferon overexpression at the RNA and protein levels to highlight its potential antitumor properties. Furthermore, RNA-seq analysis of tumor samples treated with YSCH-01 provided valuable insights into the altered gene expression profiles and signaling pathways, helping to elucidate the molecular basis of its antitumor effects. Results: Our findings demonstrated the dose-dependent infectivity of YSCH-01 in osteosarcoma cells, with varying effects observed across different cell lines. Both in vitro and in vivo studies showed that YSCH-01 effectively inhibited osteosarcoma cell proliferation. In CDX and PDX animal models, YSCH-01 exhibited potent therapeutic effects, particularly in terms of its distant effects. Additionally, IFN-αsignaling pathway was activated in the tumor tissues with YSCH-01 treatment. Conclusions: The initial findings of this study revealed the complex molecular pathways through which YSCH-01 exerts its antitumor effects in osteosarcoma. By elucidating the correlation between key molecular markers in osteosarcoma and patient outcomes, we have identified potential therapeutic targets, presenting a promising avenue for osteosarcoma treatment. Keywords: Osteosarcoma; Oncolytic Virus; YSCH-01; L-IFN.

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Phase I trial of intravenous VCN-01 oncolytic adenovirus and durvalumab in patients with head and neck metastatic squamous cell carcinoma refractory to immunotherapy

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