Novel combinatorial therapy of oncolytic adenovirus AdV5/3-D24-ICOSL-CD40L with anti PD-1 exhibits enhanced anti-cancer efficacy through promotion of intratumoral T-cell infiltration and modulation of tumour microenvironment in mesothelioma mouse model

• DOI: 10.3389/fonc.2023.1259314
• Publication Date: 2023-11-24T10:42:13Z
• Authors: Mariangela Garofalo; Magdalena Wieczorek; Ines Anders; Monika Staniszewska; Michal Lazniewski; Marta Prygiel; Aleksandra Anna Z...; Teresa Szczepińska; Dariusz Plewczynski; Stefano Salmaso; Paolo Caliceti; Vincenzo Cerullo; Ramon Alemany; Beate Rinner; Katarzyna Pancer; Lukasz Kuryk
• Keywords: Oncolytic adenovirus; Infiltration (HVAC)

Malignant mesothelioma is a rare and aggressive form of cancer. Despite improvements in cancer treatment, there are still no curative treatment modalities for advanced stage the malignancy. The aim this study was to evaluate anti-tumor efficacy novel combinatorial therapy combining AdV5/3-D24-ICOSL-CD40L, an oncolytic vector, with anti-PD-1 monoclonal antibody. vector confirmed vitro three cell lines - H226, Mero-82, MSTO-211H, subsequently antineoplastic properties combination evaluated xenograft H226 BALB/c humanized NSG mouse models. Anticancer attributed reduced tumour volume increased infiltration infiltrating lymphocytes, including activated cytotoxic T-cells (GrB+CD8+). Additionally, correlation between CD8+ lymphocytes observed. These findings were by transcriptomic analysis carried out on resected human tissue, which also revealed upregulation CD83 CRTAM, as well several chemokines (CXCL3, CXCL9, CXCL11) microenvironment. Furthermore, according observations, had strongest effect reducing mesothelin MUC16 levels. Gene set enrichment suggested that induced changes expression genes belonging "adaptive immune response" gene ontology category. Combinatorial adenovirus checkpoint inhibitors may improve anticancer survival targeted destruction triggering immunogenic death. Obtained results support further assessment AdV5/3-D24-ICOSL-CD40L therapeutic perspective treatment.