Targeted release of a bispecific fusion protein SIRPa/Siglec-10 by oncolytic adenovirus reinvigorates tumor associated macrophages to improve therapeutic outcomes in solid tumors
CD47/SIRPa and CD24/Siglec-10 signaling pathways have been found to suppress macrophage phagocytosis of malignant cells. We constructed a recombinant oncolytic adenovirus expressing a fusion protein composed of the extracellular domains of murine SIRPa and Siglec-10 (SIRPa/Siglec-10), termed AdV-mSS. Intratumoral administration of AdV-SS markedly enhanced antitumor efficacy than AdV-Ctrl in multiple solid tumor models. To reveal differences in biological processes between them. subcutaneous 14-day H22-CAR -bearing BALB/c mice were intratumorally injected with PBS, 5 × 10^8 IFU AdV-Ctrl, or 5 × 10^8 IFU AdV-mSS twice. Forty-eight hours post-treatment, we harvested tumor tissue and sorted these TAMs by anti-mouse F4/80 magnetic beads. Samples were subjected to transcriptome sequencing. Overall design: Comparative gene expression profiling analysis of RNA-seq data for TAMs from AdV-mSS (n=3) or AdV-Ctrl (n=3) or PBS (n=3) treated subcutaneous H22-CAR -bearing BALB/c mice .