Oncolytic adenovirus in treating malignant ascites: a phase II trial and longitudinal single-cell study

Mol Ther. 2024 Apr 23:S1525-0016(24)00252-1. doi: 10.1016/j.ymthe.2024.04.029. Online ahead of print.ABSTRACTMalignant ascites is a common complication resulting from the peritoneal spread of malignancies, and currently lacks effective treatments. We conducted a phase II trial (NCT04771676) to investigate the efficacy and safety of oncolytic adenovirus H101 and virotherapy-induced immune response in 25 patients with malignant ascites. Oncolytic virotherapy achieved an increased median time to repeat paracentesis of 45 days (95% confidence interval 16.5-73.5 days), compared to the preset control value of 13 days. Therapy was well-tolerated, with pyrexia, fatigue, nausea, and abdominal pain as the most common toxicities. Longitudinal single-cell profiling identified marked oncolysis, early virus replication, and enhanced CD8+ T cells-macrophages immune checkpoint crosstalk, especially in responsive patients. H101 also triggered a proliferative burst of CXCR6+ and GZMK+CD8+ T cells with promoted tumor-specific cytotoxicity. Further establishment of oncolytic virus-induced T cell expansion signature (OiTE) implicated the potential benefits for H101-responsive patients from subsequent anti-PD(L)1 therapy. Patients with up-regulated immune-signaling pathways in tumor cells and a higher proportion of CLEC10A+ DCs and GZMK+CD8+ T cells at baseline showed a superior response to H101 treatment. Our study demonstrates promising clinical responses and tolerability of oncolytic adenovirus...
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research