YSCH-01

The development of new therapies for malignant gliomas has been stagnant for decades. Through the promising outcomes in clinical trials of oncolytic virotherapy, there is now a glimmer of hope in addressing this situation. To further enhance the antitumor immune response of oncolytic viruses, we have equipped a modified oncolytic adenovirus (oAds) with a recombinant interferon-like gene (YSCH-01) and conducted a comprehensive evaluation of the safety and efficacy of this modification compared to existing treatments.

To assess the safety of YSCH-01, we administered the oAds intracranially to Syrian hamsters, which are susceptible to adenovirus. The efficacy of YSCH-01 in targeting glioma was evaluated through in vitro and in vivo experiments utilizing various human glioma cell lines. Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide.

By modifying the E1A and adding survivin promoter, the oAds have demonstrated remarkable safety and an impressive ability to selectively target tumor cells. In animal models, YSCH-01 exhibited potent therapeutic efficacy, particularly in terms of its distant effects. Additionally, YSCH-01 remains effective in inhibiting the recurrent GBM patient-derived xenograft model.

Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites.

YSCH-01, a recombinant L-IFN oncolytic adenovirus based anticancer drug with dual anti-tumor effects, has displayed significant antitumor properties in cancer treatment. However, its specific role in osteosarcoma and the underlying mechanisms remain under studied. Therefore, we analyzed clinical samples and performed experiments using osteosarcoma cell lines in both in vitro and in vivo settings. At the RNA and protein levels, the expression of L-IFN gene carried by YSCH-01 showed the potential antitumor properties. RNA-seq analysis of tumor samples treated with YSCH-01 provided insights into the altered gene expression profiles and signaling pathways, shedding light on the molecular basis of its antitumor effects. Those findings demonstrated that YSCH-01 displayed dose-dependent infectivity with different levels of efficacy and a significant inhibition of osteosarcoma cell proliferation. In both cell line and patient derived xenograft models, YSCH-01 exhibited potent therapeutic effects with the activated type I interferon signaling pathway in tumor tissues, particularly in terms of its distant effects. Furthermore, this study found out the key signal pathways through which YSCH-01 exerts its antitumor effects in osteosarcoma, which pinpointed potential therapeutic targets by identifying the type I interferon signaling pathway as the candidate molecular markers and their correlation with patient outcomes, positioning YSCH-01 as a promising candidate for osteosarcoma treatment.